Local Coverage Determination (LCD)

Biomarkers for Oncology

L35396

Expand All | Collapse All
Proposed LCD
Proposed LCDs are works in progress that are available on the Medicare Coverage Database site for public review. Proposed LCDs are not necessarily a reflection of the current policies or practices of the contractor.

Document Note

Note History

Contractor Information

LCD Information

Document Information

Source LCD ID
N/A
LCD ID
L35396
Original ICD-9 LCD ID
Not Applicable
LCD Title
Biomarkers for Oncology
Proposed LCD in Comment Period
N/A
Source Proposed LCD
DL35396
Original Effective Date
For services performed on or after 10/01/2015
Revision Effective Date
For services performed on or after 12/13/2020
Revision Ending Date
N/A
Retirement Date
N/A
Notice Period Start Date
10/29/2020
Notice Period End Date
12/12/2020
AMA CPT / ADA CDT / AHA NUBC Copyright Statement

CPT codes, descriptions and other data only are copyright 2023 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply.

Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein.

Current Dental Terminology © 2023 American Dental Association. All rights reserved.

Copyright © 2023, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association (AHA) copyrighted materials contained within this publication may be copied without the express written consent of the AHA. AHA copyrighted materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative work without the written consent of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any product or publication; creating any modified or derivative work of the UB‐04 Manual and/or codes and descriptions; and/or making any commercial use of UB‐04 Manual or any portion thereof, including the codes and/or descriptions, is only authorized with an express license from the American Hospital Association. The American Hospital Association (the "AHA") has not reviewed, and is not responsible for, the completeness or accuracy of any information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this material, or the analysis of information provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products and services are not endorsed by the AHA or any of its affiliates.

Issue

Issue Description
Issue - Explanation of Change Between Proposed LCD and Final LCD

CMS National Coverage Policy

This LCD supplements but does not replace, modify or supersede existing Medicare applicable National Coverage Determinations (NCDs) or payment policy rules and regulations for biomarkers for oncology services. Federal statute and subsequent Medicare regulations regarding provision and payment for medical services are lengthy. They are not repeated in this LCD. Neither Medicare payment policy rules nor this LCD replace, modify or supersede applicable state statutes regarding medical practice or other health practice professions acts, definitions and/or scopes of practice. All providers who report services for Medicare payment must fully understand and follow all existing laws, regulations and rules for Medicare payment for biomarkers for oncology services and must properly submit only valid claims for them. Please review and understand them and apply the medical necessity provisions in the policy within the context of the manual rules. Relevant CMS manual instructions and policies may be found in the following Internet-Only Manuals (IOMs) published on the CMS Web site.

IOM Citations:

  • CMS IOM Publication 100-02, Medicare Benefit Policy Manual,
    • Chapter 15, Section 80.1 Clinical Laboratory Services
  • CMS IOM Publication 100-03, Medicare National Coverage Determinations (NCD) Manual,
    • Chapter 1, Part 2, Section 90.2 Next-Generation Sequencing for Patients with Advanced Cancer
    • Chapter 1, Part 4, Section 210.3 Colorectal Cancer Screening Tests
  • CMS IOM Publication 100-08, Medicare Program Integrity Manual,
    • Chapter 3, Section 3.4.1.3 Diagnosis Code Requirements, Section 3.6.2.3 Limitations of Liability Determinations
    • Chapter 13, Section 13.5.4 Reasonable and Necessary Provisions in an LCD 

Social Security Act (Title XVIII) Standard References:

  • Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states that no Medicare payment shall be made for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury.
  • Title XVIII of the Social Security Act, Section 1862(a)(7). This section excludes routine physical examinations.

Code of Federal Regulations (CFR) References:

  • CFR, Title 42, Volume 2, Chapter IV, Part 410.32(d)(3) Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Coverage Guidance

Coverage Indications, Limitations, and/or Medical Necessity

Compliance with the provisions in this policy may be monitored and addressed through post payment data analysis and subsequent medical review audits.

History/Background and/or General Information

The emergence of personalized laboratory medicine has been characterized by a multitude of testing options which can more precisely pinpoint management needs of individual patients. As a result, the growing compendium of products described as biomarkers requires careful evaluation by both clinicians and laboratorians as to what testing configurations are reasonable and necessary under the Medicare Act. There are a plethora of burgeoning tools, including both gene-based (genomic) and protein-based (proteomic) assay formats, in tandem with more conventional (longstanding) flow cytometric, cytogenetic, etc. biomarkers. Classified somewhat differently, there are highly-diverse approaches ranging from single mutation biomarkers to multiple biomarker platforms, the latter of which often depend upon sophisticated biomathematical interpretative algorithms.

The term “biomarker” refers to a broad subcategory of medical signs (i.e., objective indications of medical state observed from outside the patient) which can be measured accurately and reproducibly. Medical signs stand in contrast to medical symptoms, which are limited to indications of health or illness perceived by the patient. In 1998, the National Institute of Health (NIH) defined a biomarker as: "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes pathogenic processes, or pharmacologic response to a therapeutic intervention."

This current LCD focuses upon selected testing in oncology, with some emphasis upon applying the revised 2016 CPT molecular coding format. The LCD primarily applies to molecular biomarker testing but does involve some other types of related biomarker testing, such as proteomics.

There are separate Local Coverage Determinations (LCDs) that address other biomarkers, which include a multitude of assays which are not specifically discussed below. (Please refer to the Novitas website at www.novitas-solutions.com for a complete listing of LCDs.)

Local Medicare coverage of such biomarkers must be predicated upon four fundamental principles:

  1. First, the biomarkers must have proven clinical validity/utility (CVU). 
  2. Second, to support the medical necessity of the service, there must be acceptance/uptake of specific testing into patient management. It is essential that physicians be familiar enough with all specific biomarkers, which they order, such that all test results may become clinically actionable.
  3. Providers managing oncological conditions must demonstrate that the use of biomarkers will be used to assist in the management/treatment of the beneficiary.
  4. Peer-reviewed full manuscript evidence is required to support combination panels for multiple biomarkers, particularly regarding their alleged composite clinical validity/utility. For example; such potential billing for multiple, diverse biomarkers (e.g., diagnostic/monitoring/prognostic/predictive) can only achieve medical necessity when it is clearly evident how each requested biomarker can be individually contributory.

It is useful to categorize oncology biomarkers into functional clusters which reflect both (1) The predominant intent of testing (with the caveat that individual assays may cross over into more than one category) and (2) the relative evidentiary expectations:

  1. Oncology Biomarkers Used for Diagnosis/Classification/Monitoring/Surveillance: These types of assays are supportable by case-control sensitivity/specificity studies, with appropriate designs in place to minimize the extent of bias and confounding.
  2. Oncology Biomarkers Used for Prognosis/Prediction: Oncology biomarkers used for prognosis/prediction (i.e., a predictive biomarker is associated with response [benefit] or lack of response to a particular therapy, relative to other available therapy, whereas a prognostic biomarker provides information on the likely outcome of the disease in an untreated individual).

There is a complex and diverse set of study methods which can drive the robust formulation of evidence for such esoteric testing, which are well-summarized by Deverka et al. at the Center for Medical Technology Policy, but there are currently NO standardized thresholds or benchmarks for evaluating the CVU/medical necessity of emerging biomarkers. However, the following sources (although not exhaustive and complete) may help support CVU when requesting reconsideration for coverage of biomarkers that are not included in this LCD:

  1. FDA labeling documentation.
  2. National Comprehensive Cancer Network (NCCN) Biomarkers Compendium recommendations, particularly where Category 1 evidence is noted.
  3. Findings from well-established, independent technology assessments (e.g., Evaluation of Genomic Applications in Practice and Prevention [EGAPP], Agency for Healthcare Research and Quality [AHRQ], Blue Cross and Blue Shield Association Technology Evaluation Center [BCBSA TEC] and the Cochrane Collaboration).
  4. Other independent, objective evaluations or systematic literature reviews, which can substantively contribute to the evidence base, including, but not restricted to, emerging National Institutes of Health (National Cancer Institute) guidelines for the accrual of genomics/proteomics clinical validity/utility evidence. Although there is not a prescriptive format for such systematic reviews, the documentation (submitted to Novitas) for reconsideration purposes should include the following three elements:
    • Some type of recurring/periodic Committee structure, which is comprised of at least qualified biomathematicians/methodologists, molecular pathology laboratory specialists and relevant clinicians (e.g., oncologists).
    • Evidence of active sharing of the critical evaluations in a manner that enables sufficiently broad input into this process, and a feasibly wide acceptance of this process by representative molecular pathology stakeholders. There is no preference between such a Committee being based at a single site, or even rotating among several sites.
    • Transparency of the biomarker evaluations via minutes (or a summary of minutes).


Covered Indications

MOLECULAR TESTS

Covered clinical types of application(s) are identified below as diagnostic (DX), prognostic (PROG) or predictive (PRED).

1.  Colorectal Cancer

    • KRAS (12/13) - PRED of resistance to an anti-EGFR agent
    • KRAS codon 61 - PRED of resistance to an anti-EGFR agent
    • KRAS codon 146 - PRED of resistance to an anti-EGFR agent
    • NRAS - PRED of resistance to an anti-EGFR agent
    • BRAF - PRED of resistance to an anti-EGFR agent + DX (sporadic vs. Lynch syndrome)
    • PIK3CA - PRED of resistance to an anti-EGFR agent + PROG for local recurrence
    • MSI by PCR - PRED of 5-FU resistance + DX
    • MLH1 promoter hypermethylation - PRED of 5-FU resistance + DX
    • mRNA (oncotype-Colon) – PRED for the recurrence risk for patients with Stage II colon cancer
    • Hereditary colon cancer disorders
    • Sept9

ColonSeq®

This testing provides information to the patient and provider regarding potential treatment options and implications for RAS and BRAF mutations.

Please refer to DA52986-Billing and Coding: Biomarkers for Oncology regarding coding and billing information.

2.  Non-Small Cell Lung Cancer (NSCLC)

    • EGFR- PRED of anti-EGFR response
    • KRAS (12/13) - PRED of anti-EGFR resistance
    • KRAS codon 61 - PRED of anti-EGFR resistance
    • KRAS codon 146 - PRED of anti-EGFR resistance
    • BRAF - PROG + PRED for anti-RAF inhibitor

      ThermoFisher Oncomine DX Target Test for Non-Small Cell Lung Cancer (NSCLC) is a 23 gene panel including a 3 gene target test (companion test) approved by the FDA in June 2017 for NSCLC from tissue specimens.  It can simultaneously identify the three gene variants that are a key to targeted therapy selection: BRAF and ROS1, and EGFR.  The targeted therapies are dabrafenib (Tafinlar) in combination with trametinib (Mekinist), crizotinib (Xalkori), and gefitinib (Iressa), respectively.  These three drugs are approved therapies for NSCLC patients with the above gene variants. Oncomine DX Target Test is the only FDA approved companion test that detects ROS1 fusions and that detects BRAF V600E, but it does not detect ALK fusions. Coverage is limited as specified in NCD 90.2, Next Generation Sequencing (NGS) for Patients with Advanced Cancer. Please refer to the NCD at https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=372&ncdver=1&bc=AAAAQAAAAAAA for full coverage details.

LungSeq®

Testing for genetic alteration in these genes can determine targeted therapy options that have the potential to decrease tumor burden, decrease symptoms, increase survival, and dramatically improve the quality of life for patients with specific genetic alterations.

Please refer to A52986, Billing and Coding: Biomarkers for Oncology regarding coding and billing information.

3.  Melanoma

    • BRAF - PRED of response to Vemurafenib
    • KIT - PRED of response to Imatinib (TKI)
    • NRAS - PROG + PRED for anti-MEK inhibitor
  •  
    4.  Uveal Melanoma
    • GNAQ – PROG
    • GNA11 - PROG 

5.  Brain

    • BRAF - PRED
    • EGFR - PRED
    • MGMT - PRED
    • IDH1 - DX + PROG
    • IDH2 - DX + PROG
    • PIK3CA - PRED
    • PTEN - PRED
    • CIMP - PRED
    • TERT - DX

6.  Thyroid

    • BRAF - DX + PRED
    • KRAS - PRED for Selumetinib
    • HRAS - PRED for Selumetinib
    • NRAS - PRED for Selumetinib
    • PIK3CA - PRED
    • RET - DX
    • PAX8/PPARG- DX

ThyraMIR Thyroid miRNA classifier (aPCR based microRNA gene expression classifier) (PRED) evaluates the expression levels of 10miRNA genes within an FNA biopsy: miR-29b-1-5p, miR-31-5p, miR-138-1-3p, miR-139-5p, miR-146b-5p, miR-155, miR-204-5p, miR-222-3p, miR-375, and miR-551b-3p.

Oncology Thyroid, provides gene expression analysis of 142 genes utilizing fine needle aspirate, algorithm reported as a categorical result (Afirma - PRED).

ThyraMIR is used as a companion test to ThyGeNEXT when ThyGeNEXT results are inconclusive.

      • ThyraMIR, ThyGeNEXT and Afirma services will be considered reasonable and necessary for patients with any of the following conditions:

        • An indeterminate pathology on fine needle aspiration
        • Patients with one or more thyroid nodules with a history or characteristics suggesting malignancy such as:
          • Nodule growth over time
          • Family history of thyroid cancer
          • Hoarseness, difficulty swallowing or breathing
          • History of exposure to ionizing radiation
          • Hard nodule compared with rest of gland consistency
          • Presence of cervical adenopathy
      • RosettaGX Reveal thyroid MicroRNA test, an assay used for the classification of indeterminate thyroid nodules, will be considered reasonable and necessary when the conditions outlined above for ThyraMIR, ThyGeNEXT and Afirma are met.
      • ThyroSeq is a test utilized to better define the need for thyroid surgery and the type of such surgery. ThyroSeq will be considered reasonable and necessary when the conditions outlined above for ThyraMir, ThyGeNEXT and Afirma are met.

7.  Ovary/Fallopian Tube/Peritoneum

      • AKT1 - PRED for PI3K/AKT/mTOR inhibitors
      • BRAF - DX + PROG
      • KRAS - DX + PROG
      • MLH1 promoter hypermethylation - DX
      • MSI by PCR - DX
      • PIK3CA - PRED for PI3K/AKT/mTOR inhibitors
      • PTEN - PRED for PI3K/AKT/mTOR inhibitors
      • TP53 - DX + PROG

8.  Uterus

      • AKT1 - PRED for PI3K/AKT/mTOR inhibitors
      • BRAF - PRED
      • KRAS - PRED
      • MLH1 promoter hypermethylation - DX
      • MSI by PCR - DX
      • PIK3CA - PRED for PI3K/AKT/mTOR inhibitors
      • PTEN - PRED for PI3K/AKT/mTOR inhibitors + DX + PROG
      • TP53 - DX + PROG

9.  Urinary Tract

      • FGFR3 - PROG
      • MSI by PCR - DX
      • MLH1 promoter hypermethylation - DX

10.  Prostate

      • The PROGENSA® PCA3 Assay (PRED) is an FDA-approved, automated molecular test (assay) that helps physicians determine the need for repeat prostate biopsies in men who have had a previous negative biopsy.
      • PTEN – PROG and THER
      • RB1 – DX and PROG
      • TP53 - PROG

11.  Gastrointestinal Stomal Tumor

      • KIT - PRED for Sumatinib + DX
      • PDGFRA - PRED for Sumatinib + DX

12.  Cancer of Unknown Primary (CUP)

      Molecular testing, using the Rosetta Cancer Origin Test™ (PROG), is considered reasonable and necessary in the pathologic diagnoses of CUP when a conventional surgical pathology/imaging work-up is unable to identify a primary neoplastic site. Other applications of this technology are considered not reasonable and necessary and are considered investigational in the use of diagnosis of specific tumor types such as NSCLC and renal cancers.
      TUO CTID (Cancer Type ID) (DX) is considered reasonable and necessary in the pathologic diagnoses of CUP when a conventional surgical pathology/imaging work-up is unable to identify a primary neoplastic site. Other applications of this technology are considered not reasonable and necessary and are considered investigational in the use of diagnosis of specific tumor types such as NSCLC and renal cancers.

13.  Leukemias and Lymphomas

      • Acute lymphoid leukemia (ALL)
        • JAK1
        • JAK2
        • BCR/ABL1 - DX
        • ABL1 (kinase domain) - PROG
        • IGH - DX
        • TCRB - DX
        • TCRG - DX
        • TP53 - PROG
        • MLL/AF4 - DX
        • E2A/PBX1 - DX
        • ETV6/RUNX1 - DX
        • KRAS
        • NRAS
        • NOTCH1
        • FBXW7
      • Acute myeloid leukemia (AML, and including acute promyelocytic leukemia): All PROG, except where noted below.
        • TP53
        • PML/RARA - DX
        • RUNX1/RUNX1T1 - DX
        • CBFB/MYH11 - DX
        • FLT3 ITD
        • FLT3 D835
        • NPM1
        • KRAS
        • NRAS
        • KIT
        • CEBPA
        • IDH1
        • IDH2
        • DNMT3A
        • JAK2 (p.V617F)
        • JAK2 (exon 12)
        • MPL
        • DEK/CAN - DX
        • ASXL1
        • EZH2
        • TET2
        • PML/RARalpha
        • U2AF1
        • SRSF2
        • ZRSR2
      • Hairy cell leukemia
        • BRAF
        • IGH somatic hypermutation - PROG
        • IGH - DX
      • Aplastic anemia
        • TCRB - DX
        • TCRG - DX
      • Burkitt’s lymphoma
        • IGH - DX
        • TP53 - PROG
      • Myeloproliferative diseases (MPD - essential thrombocytosis [ET], myelofibrosis & polycythemia vera [PV])
        • KIT
        • TP53
        • BCR/ABL1 - DX
        • JAK2 (p.V617F) - DX
        • JAK2 (exon 12) - DX
        • MPL - DX
        • CALR - DX
        • CSF3R - DX
        • ASXL1 - PROG
        • TET2 - PROG
        • EZH2 - PROG
        • Calr (exon 9)
      • Chronic myeloid leukemia (CML) and chronic myelomonocytic leukemia (CMML)
        • ABL1 T3151 – CML only
        • KRAS - PROG
        • NRAS - PROG
        • BCR/ABL1 - DX
        • ABL1 (kinase domain) - PRED for Imatinib
        • FLT3 ITD - PROG
        • FLT3 D835 - PROG
        • KIT - PROG
        • JAK2 (p.V617F) - PROG
        • JAK2 (exon 12) - PROG
      • Chronic lymphoid leukemia (CLL)
        • IGH - DX
        • IGH somatic hypermutation - PROG
        • TP53 - PROG
        • IGH direct probe method
        • BTK
        • PLCG2
        • BIRC3
        • BTK
        • NOTCH1
        • SF3B1
      • Follicular lymphoma
        • IGH/BCL2 - DX
      • Hypereosinophilia Syndrome (HES)
        • KIT (including p.D816V) - PROG + DX
        • FIP1L1/PDGFRA Fusion - DX
      • Mantle cell lymphoma
        • CCND1/IGH - DX
      • Mastocytosis
        • KIT (including p.D816V) - PROG + DX
        • FIP1L1/PDGFRA Fusion - DX
        • TCRG - DX
      • T-cell prolymphocytic leukemia
        • JAK1
        • JAK3
        • TCRB - DX
        • TCRG - DX
      • T-cell large granular lymphocytic leukemia(TLGLL)
        • STAT3
        • STAT5B
      • Myelodysplastic syndrome (MDS): All below biomarkers are PROG.
        • FLT3 ITD
        • FLT3 D835
        • NPM1
        • KRAS
        • NRAS
        • KIT
        • CEBPA
        • IDH1
        • IDH2
        • DNMT3A
        • JAK2 (p.V617F)
        • JAK2 (exon 12)
        • MPL
        • ASXL1
        • EZH2
        • TET2
      • Cytogenomic microarray analysis, or alternatively, a single nucleotide polymorphism (SNP) array for the same testing, is covered for the identification of various mutations. These tests are used in the diagnosis/prognosis of various hematological malignancies.

      • Waldenstrom's Lymphoplasmacytic Lymphoma
        • MYD88

14.  Myeloma Gene Expression Profile (MyPRS) (PROG) isolates plasma cells from myeloma patients, extracts DNA, which is then subjected to MicroArray testing and application of validated software programs to identifying patterns of genetic abnormalities. Seventy highly predictive genes have been identified and correlated to myeloma early relapse. MyPRS gives a predictive risk signature as high-risk or low-risk at this time. A high risk score predicts a less than 20% three-year complete remission where as a low-risk predicts a five-year complete remission of greater than 60%. The predictive value for the stratification of therapeutic interventions allows these patients to be treated in a more personalized manner based on their own genetic profile.

This test is considered reasonable and necessary only after the initial diagnosis of multiple myeloma has been made and will be available to be used in the stratification of therapeutic interventions. It would be inappropriate to use this test as a diagnostic tool or as a monitoring device of ongoing therapy. Other testing is available for this function.

The coverage is set to include only two clinical settings:

    • Once after initial diagnosis is made. In the event MyPRS was not tested at diagnosis of myeloma and there is ongoing initial therapy with persistent disease, MyPRS can be done still as an initial test.

      OR

    • If relapse has occurred and a change in the therapeutic modalities is contemplated.

Please refer to the limitations section of this policy for frequency limitations.

15.  Hereditary neuroendocrine tumor disorders - Must include 6 genes with genomic sequence analysis NEX GEN including:

    • MAX
    • SDHB
    • SDHC
    • SDHD
    • TMEM127
    • VHL

Please refer to the limitations section of this policy for frequency limitations.

16.  Hereditary neuroendocrine tumor disorders; duplication/deletion analysis panel - must include analysis for:

    • SDHB
    • SDHC
    • SDHD
    • VHL

17. Neuroendocrine Tumors

    • MGMT - PROG
    • PTEN – PROG and THER
    • RB1 – DX and PROG
    • TP53 – DX and PROG
    • TSC2 - PROG

18.  Prosigna breast cancer gene signature assay (PROG)


Background

Women with early breast cancer and up to 3 locally positive lymph nodes whose tumor is estrogen-receptor positive will usually receive anti-hormonal therapy such as tamoxifen or aromatase inhibitors. U.S. (NCCN) and international (St. Gallen) guidelines predicate the decision for adjuvant chemotherapy on the size and grade of the breast cancer and other factors including genomic assays that provide additional information on risk of recurrence (Hernandez-Ava et al., 2013). According to a 2014 review, “Prognostic factors provide an indication of whether a patient needs subsequent therapy.” (Paoletti & Hayes, 2014). Similarly, another 2014 review article states, “Efforts should be focused on reducing chemotherapy in patients unlikely to benefit.” (Rampurwala et al., 2014).

The PAM50 breast cancer gene signature test was developed in the late 1990s and initial studies showed a strong correlation with breast cancer recurrence and with complete pathologic response to neoadjuvant chemotherapy (Parker et al., 2009). While test results are reported on a scale of 1-100 as a Risk of Recurrence (ROR) score, the underlying algorithm is also able to classify cases into the luminal A and B, Her2neu, and triple-negative subtype classifications.

The Nanostring nCounter® nucleic acid analysis system replicates the PAM50 algorithm, as an FDA cleared kit, the Prosigna Breast Cancer Gene Signature Assay (FDA, 2013). The Prosigna package insert was most recently updated in January, 2015 (FDA, 2015) reflecting additional studies (Sestak et al., 2014). Notably, the Prosigna platform and the original PAM50 platform have a 0.997 correlation (Dowsett et al., 2013).

For the FDA, the Prosigna test was validated in a large population of post-menopausal, estrogen-receptor positive women based on 1,017 cases of the TransATAC study (Dowsett et al., 2013). The study showed a strong correlation with long-term breast cancer recurrence and added substantial additional prognostic information over a clinical treatment score based on standard clinical variables. This study was replicated in an independent population, also on the Prosigna test, using 1,620 samples from the ABCSG8 trial (Gnant, 2014). A separate analysis of these trials validated prediction of distant recurrence in years 5-10 after initial diagnosis (Sestak et al., 2014) and has been incorporated in the FDA labeling (FDA, 2015). The Prosigna test is issued as separate reports, consistent with FDA review and labeling, for node-negative and node-positive (1-3 node) populations. Analytic performance, precision, reproducibility, and analysis of the clinical validations are provided in the FDA labeling (https://www.accessdata.fda.gov/cdrh_docs/reviews/K130010.pdf).

Clinical utility of this breast cancer gene signature has also been assessed. The study of Martin et al. (2015) showed a 20% decision impact on decisions for or against adjuvant chemotherapy in an all-comers population of 200 new cases of incident breast cancer, when Prosigna test information became available after all other clinical information had been considered. The net rates of selecting adjuvant chemotherapy for low, intermediate, and high risk cases was similar to that observed in a meta-analysis of Oncotype DX decision data (Carlson & Roth, 2013). Additional support for the use of these test results in treatment decisions comes from Parker et al. (2009), in which there was a strong association with neoadjuvant chemotherapy response. Low-scoring cases have a very low chance of complete pathological response to neoadjuvant chemotherapy, while high-scoring cases approach a 50% chance of complete pathological response. The same findings have been observed for other breast cancer gene signatures based on prognostic algorithms (Chang et al., 2008). 

The Prosigna test is reasonable and necessary when performed according to the FDA label (https://www.accessdata.fda.gov/cdrh_docs/reviews/K130010.pdf).

19.  Desmoid Fibromatosi

    • CTNNB1 – DX and PROG

20. Hepatic Adenoma

    • CTNNB1 – DX and PROG

21.  Bladder

    • CDKN2A – PROG
    • FGFR1 – PROG
    • FGFR3 – PROG
    • MTOR – PROG
    • PIK3CA – DX and PROG
    • PTEN – PROG
    • RB1 – PROG
    • TP53 - PROG


NON-MOLECULAR ASSAYS

  1. The VeriStrat® assay is a mass spectrophotometric, serum-based predictive proteomics assay for NSCLC patients, where “first line” EGFR mutation testing is either wild-type or not able to be tested (e.g., if tissue might not be available). This test is a driver of therapy, most notably EGFR inhibitors such as erlotinib, and it has been validated by randomized controlled studies (Carbone et al. and Stinchecomb et al.) and physician uptake data (Akerley et al.) to support this particular coverage niche.

  2. This LCD does not address ALK and ROS1 FISH assays, which are indicated as predictive biomarkers for Crizotinib therapy, since they are currently covered assays. However, it is expected that non-molecular testing for these two biomarkers should provide adequate predictive information.

  3. FISH tests for bladder cancer are complex tests based on precision reagents, controls, and mathematical algorithms, all of which must be validated in clinical trials in order to support cutoff points for critical patient care decisions. Therefore, in each local physician’s office or laboratory, this category of testing is not easily replicated by miscellaneous research use or ASR reagents. Novitas will consider the coverage of FISH test kits based on peer-reviewed literature and approved manufacturer claims.

  4. Although multiple bladder cancer FISH tests may be covered according to the above general criteria, UroVysionTM Bladder Cancer Kit (UroVysion™ Kit) will be considered medically reasonable and necessary only when performed according to the FDA label (https://www.accessdata.fda.gov/cdrh_docs/pdf3/P030052b.pdf) as follows:

    The UroVysion Bladder Cancer Kit (UroVysion™ Kit) is designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p2l locus via fluorescence in situ hybridization (FISH) in urine specimens from persons with hematuria suspected of having bladder cancer. Results from the UroVysion Kit are intended for use, in conjunction with and not in lieu of current standard diagnostic procedures, as an aid for initial diagnosis of bladder carcinoma in patients with hematuria and subsequent monitoring for tumor recurrence in patients previously diagnosed with bladder cancer.

  5.  The OVA1™ proteomic assay (PROG) will be considered reasonable and necessary when performed according to the FDA label (https://www.accessdata.fda.gov/cdrh_docs/pdf15/K150588.pdf).

  6. The Risk of Ovarian Malignancy Algorithm (ROMA™) is a qualitative serum test (PROG) that combines the results of HE4 EIA, ARCHITECT CA 125 II ™ and menopausal status into a numerical score. ROMA™ is intended (per FDA clearance) to aid in assessing whether a premenopausal or postmenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy at surgery. ROMA™ will be considered reasonable and necessary for women who meet the FDA labeling criteria (https://www.accessdata.fda.gov/cdrh_docs/pdf10/K103358.pdf).

Limitations

Note: Please refer to the indications for any restrictions specific to the various assays. Please see NCD 90.2 for coverage details related to Next Generation Sequencing (NGS) for Patients with Advanced Cancer.

    1. Most genomic testing should be a once in a lifetime test. Documentation in the medical record should clearly support the need for repeat testing to include the following: recurrence of disease, change in behavior of disease, etc.

    2. The following tests will all be covered once per lifetime per beneficiary:
      • Brain Molecular Biomarkers
      • Hereditary neuroendocrine tumor disorders
      • Hereditary neuroendocrine tumor disorders; duplication/deletion analysis
      • ThyraMIR, Afirma, ThyGeNEXT, RosettaGX Reveal and ThyroSeq tests
        • Should the unlikely situation of a second, unrelated thyroid nodule with indetermindate pathology occur, coverage may be considered upon appeal with supporting documentation
      • TUO CTID (Caner TYPE ID)

    3. While some biomarkers have utility for testing once per lifetime, there are some tumor specific scenarios where repeat testing would be needed for assessment of response to therapy or to identify basis of disease progression. In cases with metastatic or recurrent tumors, repeat testing may be useful in determining further clinical management. Also, biomarkers such as BCR-ABL1 fusion, PML-RARA fusion are useful in monitoring response to therapy and predict a response up to four times per annum.

Notice: Services performed for any given diagnosis must meet all of the indications and limitations stated in this policy, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.

Summary of Evidence

Please refer to the “History/Background and/or General Information” section for general information on biomarkers.

Multiple sources of literature were submitted for consideration. The literature consisted of various investigational, observational, and experimental studies, as well as some letters to the editor in support of the leukemia biomarkers expansion, and ThyGeNEXT panel. The literature was reviewed; the following is a summary of the evidence submitted:

Numerous articles were submitted in support of the Leukemia biomarker expansion request. Taking into consideration the independent, objective evaluation and systematic literature review, which substantively contributed to the evidence base of the requested leukemia biomarkers and subsequently approved by the Molecular Testing Evaluation Committee (MTEC), all the requested biomarkers are considered reasonable and necessary for the listed disease states below:

  • Acute Lymphoblastic Leukemia
    • JAK1
    • JAK2
    • KRAS
    • NRAS
    • NOTCH1
    • FBXW7
  • Acute Myeloid Leukemia
    • TP53
    • U2AF1
    • SRSF2
    • ZRSR2
  • Chronic Lymphocytic Leukemia
    • BIRC3
    • BTK
    • PLCG2
    • NOTCH1
    • SF3B1
  • Chronic Myeloid Leukemia
    • ABL1 T315I
  • Hairy Cell Leukemia
    • BRAF
  • Myeloproliferative Diseases
    • KIT
    • TP53
  • Prolymphocytic Leukemia
    • JAK1
    • JAK3
  • T-cell Large Granular Lymphocytic Leukemia
    • STAT3
    • STAT5B


Consistent with the literature review, NCCN rating and quality of the evidence submitted, the following Biomarker Panel will be considered medically reasonable and necessary:

  • ThyGeNEXT

    • Xing, et al (2014),1 is a retrospective multicenter study that reviewed all known fusion and their prevalence in Papillary, poorly differentiated anaplastic, follicular, and medullary carcinomas. The study was a review and no new data was presented. The study conclusion demonstrates the prognostic value and perspectives of the utilization of gene fusions as therapeutic targets. The study conclusion is limited due to clinical utility not being achieved in reporting statistical findings, no available conflict of interest and no patient inhomogeneity. The quality of evidence for this study is moderate due to lack of peer review and the strength was conditional for the same reason.

    • Xing, et al (2015),2 is a retrospective study to investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer in 2099 patients. The study conclusion demonstrates the overall BRAF V600E mutation prevalence was 48.5%. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. The quality of evidence is high and the strength of recommendation is conditional for the population tested.

    • Labourier, et al (2015),3 is a cross-sectional cohort study conducted at 12 endocrinology centers across the United States. The study results found that mutations were detected with malignant outcome. Among mutation negative specimens, miRNA testing correctly identified 64% of malignant cases and 98% of benign cases. The diagnostic sensitivity and specificity of the combined algorithm was 89% (95% confidence intervals (CI): 73 – 97%) and 85% (95% CI: 75 – 92%), respectively. At 32% cancer prevalence, 61% of the molecular results were benign with a negative predictive value of 94% (95% CI: 85 – 98%). Independently of variations in cancer prevalence, the test increased the yield of true benign results by 65% relative to mRNA-based gene expression classification and decreased the rate of avoidable diagnostic surgeries by 69%. This was purely supposition. The authors concluded: multi-platform testing for DNA, mRNA and miRNA can accurately classify benign and malignant thyroid nodules, increase diagnostic yield of molecular cytology, and further improve the preoperative risk-based management of benign nodules with AUS/FLUS or FN/SFN cytology. The quality of evidence is moderate as this was not peer reviewed, a conflict of interest was present in that one of the authors was employed by the company, and the clinical utility is implied but not proven.

    • Giordano, et al (2014),4 is a case-control study conducted in 413 surgical cases comprising 17 distinct histopathologic categories. The study results found that, in the authors opinion, “standardized and validated multianalyte molecular panels can complement the preoperative and postoperative assessment of thyroid nodules and support a growing number of clinical and translational applications with potential diagnostic, prognostic, or theranostic utility.” The quality of evidence is moderate as this was a validation study only and the clinical utility is not addressed. There is an obvious conflict of interest in that the laboratory represented in authors of this study and the correspondence is through the laboratory.

    • Landa, et al (2013),5 is a retrospective study. The objectives of the study were: 1) to determine the prevalence of TERT promoter mutations C228T and C250T in different thyroid cancer histological types and cell lines; and 2) to establish the possible association of TERT mutations with mutations of BRAF, RAS, or RET/PTC. The study results found that TERT promoter mutations were found in 98 of 225 (44%) of specimens. TERT promoters C228T and C250T were mutually exclusive. The study conclusion demonstrates potential diagnostic, prognostic and therapeutic are suggested. TERT promoter mutations are highly prevalent in advanced thyroid cancers, particularly those harboring BRAF or RAS mutations which are most often TERT promoter wild type. Acquisition of a TERT promoter mutation could extend survival of BRAF- or RAS- driven clones and enable accumulation of additional genetic defects leading to disease progression. The quality of evidence is moderate as this is retrospective of variable tumor types and the clinical utility is only inferred.
Analysis of Evidence (Rationale for Determination)

Leukemia

The literature submitted for the addition of several biomarkers for various leukemia disease states was carefully reviewed. The literature submitted was also reviewed and approved by the Molecular Testing Evaluation Committee (MTEC). The MTEC reviews and votes on clinical requests for molecular testing based upon levels of evidence, including publications in the medical literature, and need for biomarkers in integral marker clinical trials. The MTEC is charged with establishing evidence-based standard-of-care testing, monitoring physician ordering of molecular tests, assuring documentation of medical necessity, analyzing utilization data, and reviewing outcomes data related to the use of molecular biomarkers. Taking into consideration the MTEC approval and taking into account item 4 of the General Information section of this policy, which allows for consideration of other independent, objective evaluations or systematic literature reviews, the requested leukemia biomarkers are considered reasonable and necessary.

ThyGeNEXT

The literature submitted for the requested addition of the ThyGeNEXT panel was carefully reviewed. After consideration of the literature, NCCN rating, and relevance to the Medicare population, the coverage of the ThyGeNEXT panel will be added in replace of the ThyGenX panel. The coverage of this panel is being added as there were enough genes requested in the panel achieving an NCCN 2A rating that when combined with the genes covered in the ThyGenX panel with a 2A rating, a minimum total of 51 genes achieved the NCCN rating of 2A. Further, the literature supported the clinical utility and clinical validity, and was relevant to the Medicare population.

Proposed Process Information

Synopsis of Changes
Changes Fields Changed
N/A
Associated Information
Sources of Information
Bibliography
Open Meetings
Meeting Date Meeting States Meeting Information
N/A
Contractor Advisory Committee (CAC) Meetings
Meeting Date Meeting States Meeting Information
N/A
MAC Meeting Information URLs
N/A
Proposed LCD Posting Date
Comment Period Start Date
Comment Period End Date
Reason for Proposed LCD
Requestor Information
This request was MAC initiated.
Requestor Name Requestor Letter
View Letter
N/A
Contact for Comments on Proposed LCD

Coding Information

Bill Type Codes

Code Description
N/A

Revenue Codes

Code Description
N/A

CPT/HCPCS Codes

Group 1

Group 1 Paragraph

N/A

Group 1 Codes

N/A

N/A

ICD-10-CM Codes that Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

ICD-10-CM Codes that DO NOT Support Medical Necessity

Group 1

Group 1 Paragraph:

N/A

Group 1 Codes:

N/A

N/A

Additional ICD-10 Information

General Information

Associated Information


Refer to the Local Coverage Article: Billing and Coding: Biomarkers for Oncology, (DA52986) for documentation requirements, utilization parameters and all coding information.

Sources of Information


Contractor is not responsible for the continued availability of websites listed.

Other Contractor Policies

Noridian Local Coverage Determination (LCD), DL36380 - MolDX: Breast Cancer Assay: Prosigna

Contractor Medical Directors

Bibliography

 

  1. Xing M, Liu R, Liu X, et al. BRAF V600E and TERT Promoter Mutations Cooperatively Identify the Most Aggressive Papillary Thyroid Cancer With Highest Recurrence. J Clin Oncol. 2014;32(25):2718-2726. doi:10.1200/JCO.2014.55.5094.
  2. Xing M, Alzahrani AS, Carson KA, et al. Association Between BRAF V600E Mutation and Recurrence of Papillary Thyroid Cancer. J Clin Oncol. 2015;33(1):42-50. doi:10.1200/JCO.2014.56.8253.
  3. Labourier E, Shifrin A, Busseniers AE, et al. Molecular testing for miRNA, mRNA and DNA on fine needle aspiration improves the preoperative diagnosis of thyroid nodules with indeterminate cytology. J Clin Endocrinol Metab. 2015;100(7):2743-2750. doi:10.1210/jc.2015-1158.
  4. Giordano TJ, Beaudenon-Huibregtse S, Shinde R, et al. Molecular testing for oncogenic gene mutations in thyroid lesions: a case-control validation study in 413 postsurgical specimens. Hum Pathol. 2014;45(7):1339-1347.
  5. Landa I, Ganly I, Chan TA, et al. Frequent Somatic TERT Promoter Mutations in Thyroid Cancer: Higher Prevalence in Advanced Forms of the Disease. J Clin Endocrinol Metab. 2013;98(9):E1562-E1566. doi10.1210/jc.2013-2383.
  6. National Comprehensive Cancer Network (NCCN). NCCN Guidelines® & Clinical Resources: About the NCCN Biomarkers Compendium®. https://www.nccn.org/professionals/biomarkers/default.aspx. Accessed August 12, 2019.
  7. National Comprehensive Cancer Network (NCCN). NCCN Guidelines® & Clinical Resources: NCCN Categories of Evidence and Consensus. https://www.nccn.org/professionals/physician gls/categories of consensus.aspx. Accessed August 12, 2019.
  8. JAK2 NCCN 2A rating page for ALL.
  9. JAK1 NCCN 2A rating page for ALL.
  10. Feng J, Li Y, Jia Y, et al. Spectrum of somatic mutations detected by targeted next-generation sequencing and their prognostic significance in adult patients with acute lymphoblastic leukemia. Journal of Hematology & Oncology. 2017;10(61):1-4. doi:10.1186/s13045-017-0431-1.
  11. Forero-Castro M, Robledo C, Benito R, et al. Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia. BJC. 2017;117:256-265. doi:10.1038/bjc2017.152.
  12. Herold T, Schneider S, Metzeler K, et al. Adults with Philadelphia chromosome-like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis. Haematologica. 2017;102(1):130-138.
  13. Flex E, Valentina P, Stella L, et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. JEM. 2008;206(4):751-758. doi:org/10.1084/jem.20072182.
  14. Li Q, Li B, Hu L, et al. Identification of a novel functional JAK1 S646P mutation in acute lymphoblastic leukemia. Oncotarget. 2017;8(21):34687-34697.
  15. Zhang J, Ding L, Holmfeldt L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481:157-163. doi:10.1038/nature10725.
  16. Roll JD, Reuther GW. CRLF2 and JAK2 in B-Progenitor Acute Lymphoblastic Leukemia: A Novel Association in Oncogenesis. AACR. 2010;70(19):7347-7352.
  17. Weigert O, Lane AA. Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition. JEM. 2012;209(2):259-273. doi:10.1084/jem.20111694.
  18. NCCN Biomarkers Compendium – TP53 for Acute Myeloid Leukemia
  19. Bochtler T, Granzow M, Stölzel F, et al. Marker chromosomes can arise from chromothripsis and predict adverse prognosis in acute myeloid leukemia. Blood. 2017;129(10):1333-1342. doi:10.1182/blood-2016-09-738161.
  20. Ohgami RS, Ma L, Merker JD, et al. Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1 and TET2 mutations. Mod Pathol. 2015;28(5):706-714. doi:10.1038/modpathol.2014.160.
  21. Boddu P, Kantarjian H, Ravandi F, et al. Outcomes with lower intensity therapy in TP53-mutated acute myeloid leukemia. Leuk Lymphoma. 2018:1-4. doi:10.1080/10428194.2017.1422864
  22. Rücker FG, Schlenk R, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012;119(9):2114-2121. doi:10.1182/blood-2011-08-375758.
  23. Terada K, Yamaguchi H, Ueki T, et al. Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor. Ann Hematol. 2018;97:51-61. doi:10.1007/s00277-017-3143-2.
  24. Fernandez-Pol S, Ma L, Ohgami RS, et al. Immunohistochemistry for p53 is a useful tool to identify cased of actue myeloid leukemia with myelodysplasia-related changes that are TP53 mutated, have complex karyotype, and have poor prognosis. Modern Pathology. 2017;30:382-392.
  25. Lal R, Lind K, Heltzer E, et al. Somatic TP53 mutations characterize preleukemic stem cells in acute myeloid leukemia. Blood. 2017;129(18):2587-2591. doi:10.1182/blood-2016-11-751008.
  26. Lehmann S, Bykov VJ, Ali D, et al. Targeting p53 in Vivo: A First-in-Human Study With p53-Targeting Compound APR-246 in refractory Hematologic Malignancies and Prostate Cancer. J Clin Concol. 2012;30(29):3633-3639. doi:10.1200/JCO.2011.40.7783.
  27. Deneberg S, Cherif H, Lazarevic V, et al. An open-label phase I dose-finding study of APR-246 in hematological malignancies. Blood. July 2016;6:e447. doi:10.1038/bcj.2016.60
  28. Welch JS, Petti AA, Miller CA, et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. N Engl J Med. 2016;375(21):2023-2036. doi:10.1056/NEJMcal605949.
  29. NCCN ABL1 T315I for Chronic Myeloid Leukemia
  30. Baer C, Kern W, Koch S, et al. Ultra-deep sequencing leads to earlier and ore sensitive detection of the tyrosine kinase inhibitor resistance mutation T315I in chronic myeloid leukemia. Haematologica. 2016;101(7):830-838. doi:10.3324/haematol.2016.145888.
  31. Chahardouli B, Zaker F, Mousavi SA, et al. Evaluation of T315I mutation frequency in chronic myeloid leukemia patients after imatinib resistance. Hematology. 2013;18(3):158-162.
  32. Gupta P, Kathawala RJ, Wei L, et al. PBA2, a novel inhibitor of imatinib-resistant BCR-ABL T3151 mutation in chronic myeloid leukemia. Cancer Lett. 2016;383(2):220-229. doi:10.1016/j.canlet.2016.09.025.
  33. Pagnano KB, Bendit I, Boquimpani C, et al. BCR-ABL Mutations in Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors and Impact on Survival. Cancer Invest. 2015;33(9):451-458. Doi:10.3109/07357907.2015.1065499.
  34. Soverini S, Colarossi S, Gnani A, et al. Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and317 in the BCR-ABL kinase domain. Haematologica. 2007;92(3):401-404.
  35. Zhang H, Liang Z, Hu Y, et al. The effectiveness of interferon-a combined with Imatinib in patient with chronic myeloid leukemia harboring T215I BCR-ABL1 mutation. Leuk Lymphoma. April 2018;4:1-2. Doi:10.1080/10428194.2018.1443329.
  36. Xu LP, Xu ZL, Zhang XH, et al. Allogeneic Stem Cell Transplantation for Patients with T315I BCR-ABL Mutated Chronic Myeloid Leukemia. Biol Blood Marrow Transplant. 2016;22(6):1080-1086. doi:10.1016/j.bbmt.2016.03.012.
  37. Cortes JE, Kim DW, Pinilla-Ibarz J. et al. A Phase 2 Trial of Ponatinib Chromosome-Positive Leukemias. N Engl J Med. 2013;369(19):1783-1796. doi:10.1056/NEJMoal306494.
  38. Mitchell R, Hopcroft LEM, Baquero P, et al. Targeting BCR-ABL-Independent TKI Resistance in Chronic Myeloid Leukemia by mTOR and Autophagy Inhibition. J Natl Cancer Inst. 2018;110(5):467-478. doi:10.1093/jnci/djx236.
  39. Jurcek T, Razga F, Mazancova P, et al. Prospective analysis of low-level BCR-ABL1 T315I mutation in CD34 + cells of patients with de novo chronic myeloid leukemia. Leuk Lymphoma. 2014;55(8):1915-1917. Doi:10.3109/10428194.2013.842988.
  40. NCCN BRAF for Hairy Cell Leukemia
  41. Andrulis M, Penzel R, Weichert W, et al. Application of a BRAF V600E Mutation –specific Antibody for the Diagnosis of Hairy Cell Leukemia. Am J Surg Pathol. 2012;36(12):1796-1800.
  42. Arcaini L, Zibellini S, Boveri E, et al. The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms. Blood. 2016;119(1):188-191. doi:10.1182/blood-2011-08-368209.
  43. Boyd EM, Bench AJ, van ‘t Veer MB, et al. High resolutions melting analysis for detection of BRAF exon 15 mutations in hairy cell leukaemia and other lymphoid malignancies. Br J Haematol. 2011;155(5):609-612. doi:10.1111/j.1365-2141.2011.08868.x.
  44. Tiacci E, Trifonov V, Schiavoni G, et al. BRAF Mutations in Hairy Cell Leukemia. N Engl J Med. 2011;364(24):2305-2315. doi:10.1056/JEJMoa1014209.
  45. Arora N, Nair S, Pai R, et al. V-raf murine sarcoma viral oncogene homolog B (BRAF) mutations in hairy cell leukemia. Indian J Pathol Microbiol. 2015;58(1):62-65. Doi:10.4103/0733-4929.151190.
  46. Rider T, Powell R, Gover R, et al. Molecular detection of BRAF-V600E is superior to flow cytometry for disease evaluation in hairy cell leukaemia. Hematol Oncol. 2014;32(3);158-161.doi:10.1002/hon.2097.
  47. Shao H, Calvo KR, Gronborg M, et al. Distinguishing hairy cell leukemia variant from hairy cell leukemia: Development and validation of diagnostic criteria. Leuk Res. 2013;37(4):401-409. doi:10.1016/j.leukres.2012.11.021.
  48. Dietrich S, Pircher A, Endris V, et al. BRAF inhibition in hairy cell leukemia with low-dose vemurafenib. Blood. 2016;127(23):2847-2855. doi:10.1182/blood-2015-11-680074.
  49. Tiacci E, Park JH, De Carolis, L, et al. Targeting Mutant BRAF with Vemurafenib in Relapsed or Refractory Hairy Cell Leukemia. N Engl J Med. 2015;33(18):1733-1747. doi:10.1056/JEJMoal506583.
  50. Vergote V, Dierickx D, Janssens A, et al. Rapid and complete hematological response or refractory hairy cell leukemia to the BRAF inhibitor dabrafenib. Ann Hematol. 2014;93(12):2087-2089. doi:10.1007/s00277-014-2104-2.
  51. Pettirossi V, Santi A, Imperi E, et al. BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity. Blood. 2015;125(8):1207-1216. doi:10.1182/blood-2014-10-603100.
  52. NCCN Biomarkers Compendium, 2A Rating for KIT and Myeloproliferative Neoplasms (MPN)
  53. NCCN Biomarkers Compendium, 2A Rating for TP53 and Myeloproliferative Neoplasms (MPN)
  54. Fontalba A, Real PJ, Fernandez-Luna JL, et al. Identification of c-Kit gene mutations in patients with polycythemia vera. Leuk Res. 2006;30(10):1325-1326. doi:10.1016/j.leukres.2005.12.020.
  55. Kimura A, Nakata Y, Katoh O. et al. c-Kit Point Mutation I Patients with Myeloproliferative Disorders. Leuk Lymphoma. 1997;25(3-4):281-287.
  56. Nakata Y, Kimura A, Katoh O, et al. c-kit mutation of extracellular domain in patients with myeloproliferative disorders. Br J Haematol. 1995;91(3):661-663.
  57. Siitonen T, Savolainen ER, Koistlinen P. Expression of the C-Kit Proto-Oncogene in Myeloproliferative Disorders and Myelodysplastic Syndromes. Leukemia. 1994;8(4):631-637.
  58. Harutyunyan A, Klampfl T, Cazzola M, et al. p53 lesions in leukemic transformation. N Engl J Med. 2011;364(5):488-490.
  59. Lundberg P, Karow A, Nienhold R, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014;123(14):2220-2228. doi:10.1182/blood-2013-11-537167.
  60. Rampal R, Ahn J, Abdel-Wahab, O, Nahas M, et al. Genomic and functional analysis of leukemic transformation of myeloproliferative neoplasms. Proc Natl Acad Sci USA. 2014;111(50):E5401-5410. doi:10.1073/pnas.1407792111.
  61. Tefferi A, Lasho TL, Guglielmelli P, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv. 2016;1(1):21-30. doi:10.1182/bloodadvances.2016000216.
  62. Vainchenker W, Delhommeau F, Constantinescu SN, et al. New mutations and pathogenesis of myeloproliferative neoplasms. Blood. 2011;118(7):1723-1735. doi:10.1182/blood-2011-02-292102.
  63. NCCN Biomarkers Compendium, 2A Rating for STAT3 and T-cell Large Granular Lymphocytic Leukemia
  64. NCCN Biomarkers Compendium, 2A Rating for STAT5B and T-cell Large Granular Lymphocytic Leukemia
  65. Andersson E, Kuusanmäki H, Bortoluzzi S, et al. Activating somatic mutations outside the SH2-domain of STAT3 in LGL leukemia. Leukemia. 2016;30(5):1204-1208. doi:10.1038/leu.2015.263.
  66. Bilori B, Thota S. Clemente MJ, et al. Tofacitinib as a novel salvage therapy for refractory T-cell large granular lymphocytic leukemia. Leukemia. 2015;29(12):2427-2429. doi:10.1038/leu.2015.280.
  67. Fasan A, Kern W, Grossman V, et al. STAT3 mutations are highly specific for large granular lymphocytic leukemia. Leukemia. 2013;27(7):1598-1600. doi:10.1038/leu.2012.350.
  68. Koskela HL, Eldfors S, Ellonen P, et al. Somatic STAT3 Mutations in Large Granular Lymphocytic Leukemia. N Engl J Med. 2012;366(20):1905-1913.
  69. Kristensen T, Larsen M, Rewes A, et al. Clinical relevance of sensitive and quantitative STAT3 mutation analysis using next-generation sequencing in T-cell large granular lymphocytic leukemia. J Mol Diagn. 2014;16(4):382-392. doi:10.1016/j.jmoldx.2014.02.005.
  70. Loughran TP, Zickl L, Olson TL, et al. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia. 2015;29(4):886-894. doi:10.1038/leu.2014.298.
  71. Morgan EA, Lee MN, DeAngelo DJ, et al. Systematic STAT3 sequencing in patients with unexplained cytopenias identifies unsuspected large granular lymphocytic leukemia. Blood Adv. 2017;1(21):1786-1789. doi:10.1182/bloodadvances.2017011197.
  72. Qui ZY, Fan L, Wang R, et al. Methotrexate therapy of T-cell large granular lymphocytic leukemia impact of STAT3 mutation. Oncotarget. 2016;7(38):61419-61425.
  73. Rajala HL, Olson T, Clemente MJ, et al. The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecular marker in large granular lymphocytic leukemia. Haematologica. 2015;100(1):91-99. doi:10.3324/haematol.2014.113142.
  74. Rajala HL, Porkka K, Maciejewski JP, et al. Uncovering the pathogenesis of large granular lymphocytic leukemia-novel STAT3 and STAT5b mutations. Ann Med. 2014;46(3):144-122. doi:10.3109/07853890.2014.882105.
  75. Sanikommu SR, Clemente MJ, Chomczynski P, et al. Clinical features and treatment outcomes in large granular lymphocytic leukemia (LGLL). Leuk Lymphoma. 2018;99(2):416-422. doi:10.1080/10428194.201.1339880.
  76. Shi M, He R, Feldman AL, et al. STAT3 mutation and its clinical and histopathologic correlation in T-cell large granular lymphocytic leukemia. Hum Pathol. Mar 2018;73:74-81. doi:10.1016/j.humpath.2017.12.014.
  77. Andersson EI, Tanahashi T, Sekiguchi N, et al. High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia. Blood. 2016;128(20):2465-2468. doi:10.1182/blood-2016-06-724856.
  78. Rajala HL, Eldfors S, Kuusanmaki H, et al. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood. 2013;121(22):4541-4550. doi:10.1182/blood-2012-12-474577.
  79. Thol F, Kade S, Schlarmann C, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1 and ZRSR2 in patients with myelodysplastic syndromes. Blood. 2012;119(15):3578-3584. doi:10.1182/blood-2011-12-399337.
  80. Hou HA, Liu CY, Kuo YY, et al. Splicing after mutations predict poor prognosis in patients with de novo acute myeloid leukemia. Oncotarget. 2016;7(8):9084-9101.
  81. Damm F, Kosmider O, Gelsi-Boyer V, et al. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood. 2012;119(14):3211-3218. doi:10.1182/blood-2011-12-400994.
  82. Barbosa TC, Andrade FG, Lopes BA. Impact of mutations in FLT3, PTPN11 and RAS genes on the overall survival of pediatric B cell precursor acute lymphoblastic leukemia in Brazil. Leuk Lymphoma. 2014;55(7):1501-1509. doi:10.3109/10428194.2013.847934.
  83. Jones D, Woyach JA, Zhao W, et al. PLCG2 C2 domain mutations co-occur with BTK and PLCG2 resistance mutations in chronic lymphocytic leukemia undergoing ibrutinib treatment. Leukemia. 2017;31(7):1645-1647.
  84. Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, et al. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study. J Clin Oncol. 2013 Dec 1;31(34):4333-42.
  85. Dunna NR, Vuree S, Anuradha C, et al. NRAS Mutations in de novo acute leukemia: Prevalence and clinical significance. Indian Journal of Biochemistry & Biophysics. June 2014;51:207-210.
  86. Te Raa, GD, Derks IA, Navrkalova V, et al. The impact of SF3B1 mutations in CLL on the DNA-damage response. Leukemia. 2015;29(5):1133-1142. doi:10.1038/leu.2014.318.
  87. Woyach JA, Bojnik E, Ruppert AS, et al. Bruton’s tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL). Blood. 2014;123(8):1207-1213. doi:10.1182/blood-2013-07-515361.
  88. NCCN Guidelines 4.2019 MS-13 Bladder Cancer
  89. Davidson PJ, McGeoch, G, Shand, B. Inclusion of a molecular marker of bladder cancer in a clinical pathway for investigation of hematuria may reduce the need for cystoscopy. NZMJ. 2019;132(1497):55-64.
  90. Konety B, Shore N, Kader AK, et al. Evaluation of Cxbladder and Adjudication of Atypical Cytology and Equivocal Cystoscopy. European Urology 76. 2019:238-243. doi: 10.1016/j.eururo.2019.04.035.
  91. Irving J, Matheson E, Minto L, et al. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood. 2014;124(23):3420-3430. doi:10.1182/blood-2014-04-531871.
  92. Oshima K, Khiabanian H, da Silva-Almeida AC, et al. Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia. PNAS. 2016;113(40):11306-11311. doi:10.1073/pnas.1608420113.
  93. Trinquand A, Tanguy-Schmidt A, Abdelali, RB, et al. Toward a NOTCH1/FBXW7/RAS/PTEN-Based Oncogenetic Risk Classification of Adult T-Cell Acute Lymphoblastic Leukemia: A Group for Research in Adult Acute Lymphoblastic Leukemia Study. J Clin Oncol. 2013;31(34):4333-4342. doi:10.1200/JCO.2012.48.5292.
  94. Irving JA, Enshaei A, Parker CA, et al. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia. Blood. 2016;128(7):911-922. doi:10.1182/blood-2016-03-704973.
  95. Asnafi V, Buzyn A, LeNoir S, et al. NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study. Blood. 2009;113(17):3918-3924. doi:10.1182/blood-2008-10-184069.
  96. Abdelali RB, Asnafi V, Leguay T, et al. Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study. Blood. 2011;118(19):5099-5107. doi:10.1182/blood-2011-02-334219.
  97. Baldus CD, Thibaut J, Goekbuget, N, et al. Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia. Haematologica. 2009;94(10):1383-1390. doi:10.3324/haematol.2008.005272.
  98. Breit S, Stanulla M, Flohr T, et al. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood. 2006;108(4):1151-1157. doi:10.1182/blood-2005-12-4956.
  99. Jenkinson S, Koo K, Mansour MR, et al. Impact of NOTCH1/FBXW7 mutations on outcome in pediatric T-cell acute lymphoblastic leukemia patients treated on the MRC UKALL 2003 trial. Leukemia. 2013;27:41-47. doi:10.1038/leu.2012.176.
  100. Liu RB, Guo JG, Liu TZ, et al. Meta-analysis of the clinical characteristics and prognostic relevance of NOTCH1 and FBXW7 mutation in T-cell acute lymphoblastic leukemia. Oncotarget. 2017;8(39):66360-66370.
  101. Natarajan V, Bandapalli OR, Rajkumar T, et al. NOTCH1 and FBXW7 Mutations Favor Better Outcome in Pediatric South Indian T-Cell Acute Lymphoblastic Leukemia. J Pediatr Hematol Oncol. 2015;37(1):23-30.
  102. Valliyammai N, Nancy NK, Sagar TG, et al. Study of NOTCH1 and FBXW7 Mutations and Its Prognostic Significance in South Indian T-Cell Acute Lymphoblastic Leukemia. J Pediatr Hematol Oncol. 2018;40(1):1-8.
  103. Weng AP, Ferrando AA, Lee W, et al. Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia. Science. 2004;306(5694):269-271. doi:10.1126/science.1102160.
  104. Eisfeld AK, Kohlschmidt J, Mrozek K, et al. Adult acute myeloid leukemia with trisomy 11 as the sole abnormality is characterized by the presence of five distinct gene mutations: MLL-PTD, DNMT3A, U2AF1, FLT3-ITS and IDH2. Leukemia. 2016;30:2254-2258. doi:10.1038/leu.2016.196.
  105. Karimi M, Nilsson C, Dimitriou M, et al. High-throughput mutational screening adds clinically important information in myelodysplastic syndromes and secondary or therapy related acute myeloid leukemia. Haematologica. 2015;100:e225.
  106. Saygin C, Hirsch C, Przychodzen B, et al. Mutations in DNMT3A, U2AF1, and EZH2 identify intermdediate-risk acute myeloid leukemia patients with poor outcome after CR1. Blood. 2018;8(4):1-12. doi:10.1038/s41408-017-0040-9.
  107. Larsson CA, Cote G, Quintas-Cardama A. The Changing Mutational Landscape of Acute Myeloid Leukemia and Myelodysplastic Syndrome. Mol Cancer Res. 2013;11(8):815-827. doi:10.1158-1541-7786.MCR-12-0695.
  108. Lindsley RC, Mar BG, Mazzola E, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015;125(9):1367-1376. doi:10.1182/blood-2014-11-610543.
  109. Zhang S, Rampal R, Manshouri T, et al. Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome. Blood. 2012;119(9):4480-4485. doi:10.1182/blood-2011-11-390252.
  110. Zheng X, Zhan Z, Naren D, et al. Prognostic value of SRSF2 mutations in patients with de novo myelodysplastic syndromes: A meta-analysis. PLoS one. 2017;12(9):1-12. doi:10.1371/journal.pone.0185053.
  111. Alhourani E, Othman M, Melo JB, et al. BIRC3 alterations in chronic and B-cell acute lymphocytic leukemia patients. Oncol lett. 2016;11:3240-3246. doi:10.3892/ol.2016.4388.
  112. Chiaretti S, Marinelli M, Del Giudice I, et al. NOT CH1, SF3B1, BIRC3 AND TP53 mutations in patients with chronic lymphocytic leukemia undergoing first-line treatment: correlation with biological parameters and response to treatment. Leuk Lymphoma. 2014;55(12):2785-2792. doi:10.3109/10428194.2014.898760.
  113. Cortese D, Sutton LA, Cahill N, et al. On the way towards a ‘CLL prognostic index’: focus on TP53, BIRC3, SF3B1, NOTCH1 and MYD88 in a population-based cohort. Leukemia. 2014;28(3):710-713. doi:10.1038/leu.2013.333.
  114. Raponi S, Del Giudice, Ilari C, et at. Biallelic BIRC3 inactivation in chronic lyphocytic leukaemia patients with 11q deletion identifies a subgroup with very aggressive disease. Br J Haematol. 2018;185(1):156-162. doi:10.1111/bjh.15405.
  115. Rossi D, Fangazio M, Rasi S, et al. Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lyphocytic leukemia. Blood. 2012;119(12):2854-2862. doi:10.1182/blood-2011-12-395673.
  116. Rossi D, Gaidano G. Molecular genetics of high-risk chronic lymphocytic leukemia. Expert Rev Hematol. 2012;5(6):593-607. doi:10.1586/ehm.12.58.
  117. Rossi D, Rasi S, Spina V, et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood. 2013;121(8):1403-1412.
  118. Ahn IE, Underbayev C, Albitar A, et al. Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia. Blood. 2017;129(11):1469-1479. doi:10.1182/blood-2016-06-719294.
  119. Albitar A, Ma W, DeDios I, et al. Using high-sensitivity sequencing for the detection of mutations in BTK and PLCy2 genes in cellular and cell-free DNA and correlation with progression in patients treated with BTK inhibitors. Oncotarget. 2017;8(11):17936-17944.
  120. Landau DA, Sun C, Rosebrock D, et al. The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy. Nat Commun.2017;8(2185):1-12. doi:10.1038/s41467-017-02329-y.
  121. Sharma S, Galanina N, Guo A, et al. Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL. Oncotarget. 2016;7(42):68833-68841.
  122. Woyach JA, Furman RR, Liu TM, et al. Resistance Mechanisms for the Bruton’s Tyrosine Kinase Inhibitor Ibrutinib. N Engl J Med. June 2014;370:2286-2294. doi:10.1056/NEJMoal400029.
  123. Woyach JA, Ruppert AS, Guinn D, et al. BTKC481S-Mediated Resistance to Ibrutinib in Chronic Lymphocytic Leukemia. J Clin Oncol. 2017;35(13):1437-1443. doi:10.1200/JCCO.2016.70.2282.
  124. Baliakas P, Hadzidimitriou A, Sutton LA, et al. Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia. 2015;29(2):329-326.
  125. Jeromin S, Weissmann S, Haferlach C, et al. SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia. 2014;28(1):108-117. doi:10.1038/leu.2013.263.
  126. Oscier DG, Rose-Zerilli MJ, Winkelmann N, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood. 2013;121(3):468-475. doi:10.1182/blood-2012-05-429282.
  127. Puente XS, Bea S, Valdes-Mas R, et al. Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature. 2015;526:519-524 doi:10.1038/nature14666.
  128. Putowski M, Podgórniak M, Piróg M, et al. Prognostic impact of NOTCH1, MYD88, and SF3B1 mutations in Polish patients with chronic lymphocytic leukemia. Pol Arch Intern Med. 2017;127(4):238-244. doi:10.20452/pamw.3998.
  129. Stilgenbauer S, Schnaiter A, Paschka P, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014;123(21):3247-3254. doi:10.1182/blood-2014-01-546150.
  130. Quesada V, Conde L, Villamor N, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet. 2012;44(1):47-52. doi:10.1038/ng.1032.
  131. Takahashi K, Hu B, Wang F, et al. Clinical Implications of Cancer Gene Mutations in Patients with Chronic Lymphocytic Leukemia Treated with Lenalidomide. Blood. 2018;131(16):1820-1832.
  132. Wang L, Lawrence MS, Wan Y, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011;365(26):2497-2506.
  133. Bellanger D, Jacquemin V, Chopin M, et al. Recurrent JAK1 and JAK3 somatic mutations in T-cell prolymphocytic leukemia. Leukemia. 2014;28(2):417-419. doi:10.1038/leu.2013.271.
  134. Greenplate A, Wang K, Tripathi RM, et al. Genomic Profiling of T-Cell Neoplasms Reveals Frequent JAK1 and JAK3 Mutations With Clonal Evasion From Targeted Therapies. JCO Precis Oncol. 2018;(2):1-16. doi:10.1200/PO.17.00019.
  135. Kiel MJ, Velusamy T, Rolland D, et al. Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia. Blood. 2014;124(9):1460-1472. doi:10.1182/blood-2014-03-559542.
  136. Laribi K, Lemaire P, Sandrini J. et al, Advances in the understanding and management of T-cell prolymphocytic leukemia. Oncotarget. 2017;8(61):104664-104686.
  137. Bergmann AK, Schneppenheim S, Seifert M, et al. Recurrent Mutation of JAK3 in T-Cell Prolymphocytic Leukemia. Genes Chromosomes Cancer. 2014;53(4):309-316. Doi:10.1002/gcc.22141.
  138. López C, Bergmann AK, Paul U, et al. Genes encoding members of the JAK-STAT pathway or epigenetic regulators are recurrently mutated in T-cell prolymphocytic leukaemia. Br J Haematol. 2016;173(2):265-273. doi:10.1111/bjh.13952.
  139. Stengel A, Kern W, Zenger M, et al. Genetic Characterization of T-PLL Reveals Two Major Biologic Subgroups and JAK3 Mutations as Prognostic Marker. Genes Chromosomes Cancer. 2016;55(1):82-94. doi:10.1002/gcc.22313.
  140. Agrawal N, Akbani R, Aksoy B, et al. Integrated Genomic Characterization of Papillary Thyroid Carcinoma. Cell. 2014;159(3):676–690. doi:10.1016/j.cell.2014.09.050.
  141. Parameswaran R, Brooks S, Sadler GP. Molecular pathogenesis of follicular cell derived thyroid cancers. International Journal of Surgery. 2010;8(3):186-193. doi:10.1016/j.ijsu.2010.01.005.
  142. Censi S, Cavedon E, Bertazza L, et al. Frequency and Significance of Ras, Tert Promoter, and Braf Mutations in Cytologically Indeterminate Thyroid Nodules: A Monocentric Case Series at a Tertiary-Level Endocrinology Unit. Frontiers in Endocrinology. 2017;8:273. doi:10.3389/fendo.2017.00273.
  143. Wylie D, Beaudenon-Huibregtse S, Haynes BC, Giordano TJ, Labourier E. Molecular classification of thyroid lesions by combines testing for miRNA gene expression and somatic gene alterations. J Path: Clin Res. 2016;2(2):93-103. doi:10.1002/cjp2.38.
  144. Nikiforova MN, Wald AI, Roy S, Durso MB, Nikiforov YE. Targeted Next-Generation Sequencing Panel (ThyroSeq) for Detection of Mutations in Thyroid Cancer. J Clin Endocrinol Metab. 2013;95(11):E1852-E1860. doi:10.1210/jc.2013-2292.
  145. Nikiforov YE, Carty SE, Chiosea SI, et al. Highly Accurate Diagnosis of Cancer in Thyroid Nodules With Follicular Neoplasm/Suspicious for a Follicular Neoplasm Cytology by ThyroSeq v2 Next-Generation Sequencing Assay. Cancer. 2014;120(23):3627-3634. doi:10.1002/cnrc.29038.
  146. Steward DL, Carty SE, Sippel RS, et al. Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology A Prospective Blinded Multicenter Study. JAMA Oncol. 2019;5(2):204-212. doi:10.1001/jamaoncol.2018.4616.
  147. Murugan AK, Xing M. Anaplastic Thyroid Cancers Harbor Novel Oncogenic Mutations of the ALK Gene. American Association for Cancer Research. 2011;71(13):4403-4411. doi:10.1158/0008-5472.CAN-10-4041.
  148. Yakushina VD, Lerner LV, Lavrov AV. Gene Fusions in Thyroid Cancer. Thyroid. 2018;28(2):158-167. doi:10.1089/thy.2017.0318.
  149. Liu X, Bishop J, Shan Y. et al. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocrine-Related Cancer. 2013;20(4):603-610. doi:10.1530/ERC-13-0210.
  150. Melo M, da Rocha AG, Vinagre J, et al. TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas. J Clin Endocrinol Metab. 2014;99(5):E754-E765. doi:10.1210/jc.2013-3734.
  151. Liu R, Bishop J, Zhu G, Zhang T, Ladenson P, Xing M. Mortality Risk Stratification by Combining BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Cancer Genetic Duet of BRAF and TERT Promoter Mutations in Thyroid Cancer Mortality. JAMA Oncol. 2017;3(2):202-208. doi:10.1001/jamaoncol.2016.3288.
  152. Liu R, Xing M. TERT promoter mutations in thyroid cancer. Endocrine-Related Cancer. 2016;23(3):R143-R155. doi:10.1530/ERC-15-0533.
  153. Stransky N, Cerami E, Schalm S, Kim J, Lengauer C. The landscape of kinase fusions in cancer. Nature Communications. 2014;5(4846):1-10. doi:10.1038/ncomms5846.
  154. Ricarte-Filho JC, Ryder M, Chitale DA, et al. Mutational Profile of Advanced Primary and Metastatic Radioactive Iodine-Refractory Thyroid Cancers Reveals Distinct Pathogenetic Roles for BRAF, PIK3CA, and AKT1. American Association for Cancer Research. 2009;69(11):4885-4893. doi:10.1158/0008-5472.CAN-09-0727.
  155. Wu G, Mambo E, Guo Z, et al. Uncommon Mutation, but Common Amplifications, of the PIK3CA Gene in Thyroid Tumors. J Clin Endocrinol Metab. 2005;90(8):4688-4693: doi:10.1210/jc.2004-2281.
  156. Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime Cancer Risks in Individuals with Germline PTEN Mutations. Clin Cancer Res. 2012;18(2):400-407. doi:10.1158/1078-0432.CCR-11-2283.
  157. Dahia PLM, Marsh DJ, Zheng Z, et al. Somatic Deletions and Mutations in the Cowden Disease Gene, PTEN, in Sporadic Thyroid Tumors. Cancer Res. 1997;57(21):4710-4713.
  158. Hsiao SJ, Nikiforov YE. Molecular approaches to thyroid cancer diagnosis. Endocrine-Related Cancer. 2014;21(5):T301-T313. doi:10.1530/ERC-14-0166.
  159. Jang EK, Song DE, Sim SY, et al. NRAS Codon 61 Mutation Is Associated with Distant Metastasis in Patients with Follicular Thyroid Carcinoma. Thyroid. 2014;24(8):1275-1281. doi:10.1089/thy.2014.0053.
  160. Cantara S, Capezzone M, Marchisotta. Et al. Impact of Proto-Oncogene Mutation Detection in Cytological Specimens from Thyroid Nodules Improves the Diagnostic Accuracy of Cytology. J Clin Endocrinol Metab. 2010;95(3):1365-1369. doi:10.1210/jc.2009-2103.
  161. Wohllk N, Cote GJ, Bugalho MMJ, et al. Relevance of RET Proto-Oncogene Mutations in Sporadic Medullary Thyroid Carcinoma. J Clin Endocrinol Metab. 1996;81(10):3740-3745.
  162. Marsh DJ, Learoyd DL, Andrew SD, et al. Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinoma. Clinical Endocrinology. 1996;44(3):249-257.
  163. Swierniak M, Pfeifer A, Stokowy T, et al. Somatic mutation profiling of follicular thyroid cancer by next generation sequencing. Molecular and Cellular Endocrinology. June 2016;433:130-137. doi:10.1016/j.mce.2016.06.007.
  164. Yin D, Yu K, Lu R, et al. Clinicopathological significance of TERT promoter mutation in papillary thyroid carcinomas: a systematic review and meta-analysis. Clinical Endocrinology. 2016;85:299-305. doi:10.1111/cen.13017.
  165. NCCN Guidelines Version 4.2019 Bladder Cancer
  166. American College of Medical Genetics and Genomics and American Board of Internal Medicine. Making smart decisions about genetic testing. Choosing Wisely. https://www.choosingwisely.org/patient-resources/making-smart-decisions-about-genetic-testing/. Published October 2015. Accessed September 30 2019.
  167. Abdul-Maksoud RS, Shalaby SM, Elsayed WS, et al. Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer. Gene. 2016; 591: 320-326.
  168. Abraham D, Jackson N, Gundara JS, et al. MicroRNA profiling of sporadic and hereditary medullary thyroid cancer identifies predictors of nodal metastasis, prognosis, and potential therapeutic targets. Clinical Cancer Research. 2011; 1: 4772–4781.
  169. Abubaker J, Jehan Z, Bavi P, et al. Clinicopathological Analysis of Papillary Thyroid Cancer with PIK3CA Alterations in a Middle Eastern Population. J Clin Endocrinol Metab. 2008; 93(2): 611-618.
  170. Akerley WL, Nelson RE, Cowie RH, et al. The Impact of Serum based Proteomic Mass Spectrometry Test on Treatment Recommendations in Advanced Non Small Cell Lung Cancer. Current Medical Research & Opinion. 2013; 29(5): 517-25.
  171. Al-Ahmadie HA, Iyer G, Janakiraman M, et al. Somatic mutation of fibroblast growth factor receptor-3 (FGFR3) defines a distinct morphological subtype of high-grade urothelial carcinoma. J Pathol. 2011; 224: 270-279.
  172. Albain K, Barlow W, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, estrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomized trial. Lancet Oncol. 2010; 11: 55-65.
  173. Albitar M, Manshouri, Kantarjian H, et al. Correlation between Lower C-MPL Protein Expression and Favorable Cytogenetic Groups in Acute Myeloid Leukemia. Leukemia Research. 1999; (23): 63-69.
  174. Alexander EK, Kennedy GC, Zubair WB, et al. Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate Cytology. New England Journal of Medicine. 2012; 367: 705-15.
  175. Alexander EK, Schorr M, Klopper J, et al. Multi-center experience with the Afirma Gene Expression Classifier. Journal of Clinical Endocrinology Metabolism. 2014; 99(1): 119-25.
  176. Ali SZ, Cibas ES. The Bethesda System for Reporting Thyroid Cytopathology. Definitions, criteria and explanatory notes. New York, Springer. 2010.
  177. Allegra C, Jessup J, Somerfield R, et al. American Society of Clinical Oncology Provisional clinical Opinion: Testing for KRAS Gene Mutations in Patients with Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy. Journal of Clinical Oncology. 2009; 27 (12): 2091-2096.
  178. An HJ, Kim KI, Kim JY, et al. Microsatellite Instability in Endometrioid Type Endometrial Adenocarcinoma is Associated With Poor Prognostic Indicators. Am J Surg Pathol. 2007; 31: 846-853.
  179. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004; 350(23): 2343-2351.
  180. Andre T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009; 27: 3109-3116.
  181. Aparicio AM, Shen L, Tapia EL, et al. Combined tumor suppressor defects characterize clinically defined aggressive variant prostate cancers. Clin Cancer Res. 2016; 22(6): 1520-1530.
  182. Arcila ME, Chaft JE, Nafa K, et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res. 2012; 18(18): 4910-4918.
  183. Arcila M, Drilon A, Sylvester B, et al. MAP2K1 (MEK1) mutations define a distinct subset of lung adenocarcinoma associated with smoking. Author manuscript. Clin Cancer Res. 2015: 21(8): 1935-1943.
  184. Asari R, Passler C, Kaczirek K, et al. Hypoparathyroidism After Total Thyroidectomy: A Prospective Study. Archives of Surgery. 2008; 143(2): 132-137.
  185. Asnis-Alibozek A, Fine M, Russo P, et al. Cost of Care for Malignant and Benign Renal Masses. The American Journal of Management Care. 2013; 19(8): 617-624.
  186. Avet-Loiseau H, Li C, Magrangeas F, et.al. Prognostic significance of copy-number alterations in multiple myeloma. J. Clin. Oncol. 2009; 27: 4585-4590.
  187. Bacher U, Kern W, Haferlach C, et al. Cyclin D1 (CCND1) Messenger RNA Expression as Assessed by Real-Time PCR contributes to Diagnosis and Follow-up Control in Patients with Mantle Cell Lymphoma. Experimental Hematology. 2013; 41(12): 1028-1037.
  188. Bae JS, Kim Y, Jeon S, et al. Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation. Diagnostic Pathology. 2016;11(21): 1-10.
  189. Bagrodia A, Cha EK, Sfakianos JP, et al. Genomic biomarkers for the prediction of stage and prognosis of upper tract urothelial carcinoma. Author manuscript. J Urol. 2016; 195(6): 1684-1689.
  190. Baik CS, Myall NJ,and Wakelee HA. Targeting BRAF-Mutant Non-Small Cell Lung Cancer: From Molecular Profiling to Rationally Designed Therapy. The Oncologist. 2017;22: 786-796.
  191. Bain B. Myeloid and Lymphoid Neoplasms with Eosinophilia and Abnormalities of PDGFRA, PDGFRB or FGFR1. Haematologica. 2010; 95: 696-698.
  192. Bains A, Luthra R, Medeiros L, Zuo Z. FLT3 and NPM1 Mutations in Myelodysplastic Syndromes: Frequency and Potential Value for Predicting Progression to Acute Myeloid Leukemia. Am J Clin Pathol. 2011; 135: 62-69.
  193. Ball DW. Medullary Thyroid Cancer: Monitoring and Therapy. Endocrinology Metabolism Clin North Am. 2007; 36(3): 823–837.
  194. Balschun K, Haag J, Wenke A K, et al. KRAS, NRAS, PIK3CA Exon 20, and BRAF Genotypes in Synchronous and Metachronous Primary Colorectal Cancers, Diagnostic and Therapeutic Implications. The Journal of Molecular Diagnostics. 2011; 13 (4): 436-445.
  195. Baro C, Espinet B, Salido M, et al. Cryptic IGH/BCL2 Rearrangements with Variant FISH Patterns in Follicular. Leukemia Research. 2011; 35(2): 256-259.
  196. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116: 281–297.
  197. Bartoletti R, Cai T, Nesi G, et al. Loss of P16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer. J Surg Res. 2007; 143: 422-427.
  198. Base RC, Hans L, Urban N, et al. Translational Crossroads for Biomarkers. Clin Cancer Res. 2005; 11: 6103. doi: 10.1158/1078-0432.CCR-04-2213.
  199. Baysan M, Bozdag S, Cam M, et al. G-Cimp Status Prediction of Glioblastoma Samples Using mRNA Expression Data. PLOS ONE. 2012; 7 (11): 1-10.
  200. Beaudenon-Huibregtse S, Alexander EK, Guttler RB, et al. Centralized Molecular Testing for Oncogenic Gene Mutations Complements the Local Cytopathologic Diagnosis of Thyroid Nodule. Thyroid. 2014; 24(10): 1479-1487.
  201. Beltran H, Prandi D, Mosquera JM, et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nature Medicine. 2016; 22(3):298-305.
  202. Berggren P Steineck G, Adolfsson J, et al. p53 mutations in urinary bladder cancer. British Journal of Cancer. 2001; 84 (11): 1505-1511.
  203. Bergethon K, Shaw AT, Ou SHI, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30(8): 863-870.
  204. Berruti A, Amoroso V, Gallo F, et al. Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy: A meta-regression of 29 randomized prospective studies. Journal of Clinical Oncology. 2014; 32(34): 3883-3891.
  205. Besaratinia A and Pfeifer GP. Uveal melanoma and GNA11 mutations: a new piece added to the puzzle. News and Views. 2010: 18-20.
  206. Bettendorf O, Schmidt H, Staebler A, et al. Chromosomal imbalances, loss of heterozygosity, and immunohistochemical expression of TP53, RB1 and PTEN in intraductal cancer, intraepithelial neoplasia, and invasive adenocarcinoma of the prostate. Genes Chromosomes Cancer. 2008; 47: 565-572.
  207. Biekowski M, Piaskowski S, Stoczyska-Fidelus E, et al. Screening for EGFR Amplifications with a Novel Method and their Significance for the Outcome of Glioblastoma Patients. PLOS ONE. 2013; 8 (6): 1-10.
  208. Billerey C, Chopin D, Aubriot-Lorton MH, et al. Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol. 2001; 158(6): 1955-1959.
  209. Bioulac-Sage P, Sempoux C, and Balabaud C. Hepatocellular adenoma: classification, variants and clinical relevance. Seminars in Diagnostic Pathology. 2017; 34: 112-125.
  210. Birkeland E, Wik E, Mjos S, et al. KRAS gene amplification and overexpression but not mutation associates with aggressive and metastatic endometrial cancer. British Journal of Cancer. 2012; 107: 1997-2004.
  211. Bischoff J, Ignatov A, Semczuk A, et al. hMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases. Clin Exp Metastasis. 2012; 29: 889-900.
  212. Bishop JA, Benjamin H, Cholakh H, et al. Accurate Classification of Non-Small Cell Lung Carcinoma Using a Novel MicroRNA-Based Approach.Clin Cancer Res. 2010; 16(2): 610-19.
  213. Blaszyk H, Wang L, Dietmaier W, et al. Upper Tract Urothelial Carcinoma: A Clinicopathologic Study Including Microsatellite Instability Analysis. Modern Pathology. 2002; 15(8): 790-797.
  214. Bo Wu, Schoedel K, Carty S, et al. Incidental diagnosis of parathyroid lesions by preoperative use of next-generation molecular testing. World J Surg. 2018. https://doi.org/10.1007/s00268-018-4548-3
  215. Bohm MR, Tsianakas A, Merte RL, et al. Mutational analysis of GNAQ and GNA11 to aid therapy management of a choroidal melanoma metastatic to the contralateral orbit. JAMA Ophthalmol. 2013; 131(6): 812-814.
  216. Bongiovanni M, Spitale A, Faquin WC, et al. The Bethesda System for Reporting Thyroid Cythopathology: A Meta-Analysis. Acta Cytologica. 2012; 56: 333–339.
  217. Bossuyt P, Reitsma J, Linnet, K, et al. Beyond Diagnostic Accuracy: The Clinical Utility of Diagnostic Tests. Clinical Chemistry. 2012; 58(12): 1636-1643.
  218. Bouscary D, Preudhomme C, Ribrag V, et al. Prognostic value of c-mpl expression in myelodysplastic syndromes. Leukemia. 1995; 9: 783-788.
  219. Bowen D, Frew M, Hills R, et al. RAS Mutation in Acute Myeloid Leukemia is Associated with Distinct Cytogenetic Subgroups but does not Influence Outcome in Patients Younger than 60 Years. Blood. 2005; 106 (6): 2113-2119.
  220. Boyd E, Bench A, Goday-Fernandez A, et al. Clinical utility of routine MPL exon 10 analysis in the diagnosis of essential thrombocythaemia and primary myelofibrosis. British Journal of Haematology. 2010; 149: 250-257.
  221. Breen V, Kasabov N, Kamat A, et al. A holistic comparative analysis of diagnostic tests for urothelial carcinoma: a study of Cxbladder Detect, Urovysion® FISH, NMP22® and cytology based on imputation of multiple datasets. BMC Medical Research Methodology. 2015; 15:45 doi:10.1186/s12874-015-0036-8.
  222. Breyer J, Wirtz RM, Erben P, et al. High CDKN2A/p16 and low FGFR3 expression predict progressive potential of stage pT1 urothelial bladder carcinoma. Clin Genitourin Cancer. 2018: 1-9.
  223. Broderick D, Di C, Parrett T, et al. Mutations of PIK3CA in Anaplastic Oligodendrogliomas, High-Grade Astrocytomas, and Medulloblastomas. Cancer Research. 2004; 64(15): 5048-5050.
  224. Broyl A, Hose D, Lokhorst H,  et al. Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients. Blood. 2010; 116(14): 2543-2553.
  225. Brüggemann M, Gökbuget N, Kneba M. Acute Lymphoblastic Leukemia: Monitoring Minimal Residual Disease as a Therapeutic Principle. Seminars in Oncology. 2012; 39 (1): 47-57.
  226. Brüggemann M, van der Velden VHJ, Raff T, et al. Rearranged T-Cell Receptor Beta Genes Represent Powerful Targets for Quantification of Minimal Residual Disease in Childhood and Adult T-Cell Acute Lymphoblastic Leukemia. Leukemia 2004; 18: 710-719.
  227. Brustugun OT, Khattak AM, Tromborg AK, et al. BRAF-mutations in non-small cell lung cancer. Lung Cancer. 2014; 84: 36-38.
  228. Bucheit AD, Syklawer E, Jakob JA, et al. Clinical characteristics and outcomes with specific BRAF and NRAS mutations in patients with metastatic melanoma. Cancer. 2013; 119(21): 3821-9.
  229. Bullinger L, Kronke J, Schon C, et al. Identification of acquired copy number alterations and uniparental disomies in cytogenetically normal acute myeloid leukemia using high-resolution single-nucleotide polymorphism analysis. Leukemia. 2010; 24: 438-449.
  230. Burger M, van der Aa MN, van Oers JM, et al. Prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: A prospective study. Eur Urol. 2008; 54: 835-844.
  231. Burken MI, Wilson KS, Heller K, et al. The Interface of Medicare Coverage Decision-Making and Emerging Molecular-Based Laboratory Testing. Genet Med. 2009; 11(4): 225-31.
  232. Busch K, Keller T, Fuchs U, et al. Identification of Two Distinct MYC Breakpoint Clusters and their Association with Various IGH Breakpoint Regions in the t(8;14) Translocations in Sporadic Burkitt-Lymphoma. Leukemia. 2007: 1739-1751.
  233. Cabanero M, Sangha R, Sheffield BS, et al.  Management of EGFR-mutated non-small-cell lung cancer: practical implications from a clinical and pathology perspective. Curr Oncol. 2017;24(2): 111-119.
  234. Cahill S, Smyth P, Denning K, et al. Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. Molecular Cancer. 2007; 6:21.
  235. Cahill S, Smyth P, Finn SP, et al. Effect of ret/PTC 1 rearrangement on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. Molecular Cancer. 2006; 5: 70.
  236. Calin GA, Ferracin M, Cimmino A, et al. A microRNA signature associated with prognosis and progression of chronic lymphocytic leukemia. New England Journal of Medicine. 2005; 353: 1793-1801.
  237. Campana D, Walter T, Pusceddu S, et al. Correlation between MGMT promoter methylation and response to temozolmide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study. Endocrine. 2017. Doi 10.1007/s12020-017-1474-3
  238. Campanella N, De Oliveira A, Scapulatempo-Neto C, et al. Biomarkers and Novel Therapeutic Targets in Gastrointestinal Stromal Tumors (GISTs). Recent Patents on Anti-Cancer Drug Discovery. 2013; 8 (3): 288-297.
  239. Cappetta M, Perez V, Zubillaga MN, et al. Concomitant detection of BCR-ABL translocation and JAK2 V617F mutation in five patients with myeloproliferative neoplasm at diagnosis. International Journal of Laboratory Hematology. 2013; 35: e4-e5.
  240. Carbone DP, Ding K, Roder H, et al. Prognostic and Predictive Role of the Veristrat Plasma Test in Patients With Advanced Non-Small-Cell Lung Cancer Treated With Erlotinib or Placebo in the NCIC Clinical Trials Group BR.21 Trial. J Thorac Oncol. 2012; 7(11): 1653-60.
  241. Carlson J, Roth J. The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis. Breast Cancer Res and Treat. 2013; 14(1): 12-22.
  242. Care R, Valk P, Goodeve A, et al. Incidence and Prognosis of c-KIT and FLT3 Mutations in Core Binding Factor (CBF) Acute Myeloid Leukaemias. British Journal of Haematology. 2003; 121(5): 775-777.
  243. Carlson J, Roth J. The impact of the Oncotype Dx breast cancer assay in clinical practice: a systematic review and meta-analysis. Breast Cancer Res and Treat. 2013; 14(1): 12-22.
  244. Cartwright T, Chao C, Lee M, et al. Effect of the 12-gene colon cancer assay results on adjuvant treatment recommendations in patients with stage II colon cancer. Curr Med Res Opin. 2014; 30(2): 321-328.
  245. Carvajal RD, Antonescu CR, Wolchok JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011; 305(22): 2327-34.
  246. Catto JWF, Xinarianos G, Burton JL, Meuth M, Hamdy FC. Differential Expression of hMLH1 and hMSH2 is Related to Bladder Cancer Grade, Stage and Prognosis but Not Microsatellite Instability. Int J Cancer. 2003; 105: 484-490.
  247. Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer:  AUA/SUO Guideline. American Urological Association Education and Research.  2016: 1-45. 
  248. Chaux A, Comperat E, Varinot J, et al. High levels of phosphatase and tensin homolog expression are associated with tumor progression, tumor recurrence, and systemic metastases in pT1 urothelial carcinoma of the bladder: A tissue microarray study of 156 patients treated by transurethral resection. Urology. 2013; 81(1): 116-122.
  249. Chee CE, Meropol NJ. Current status of gene expression profiling to assist decision making in stage II colon cancer. Oncologist. 2014; 19(7): 704-711.
  250. Chen D, Zhang LQ, Huang JF, et al.  BRAF Mutations in Patients with Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. PLoS One. 2014;9(6): e101354.
  251. Chen H, Sippel RS, Pacak K. The NANETS Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors: Pheochromocytoma, Paraganglioma & Medullary Thyroid Cancer. Pancreas. 2010; 39(6): 775-783.
  252. Chen W, Huang Q. Detection of FLT3/ITD, JAK2(V617F) and NPM1 Gene Mutations in Chronic Myelomonocytic Leukemia. Leukemia Research. 2009; 33(11): E207-E209.
  253. Chen YT, Kitabayashi N, Zhou XK, et al. MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma. Modern Patholology. 2008; 21: 1139-1146.
  254. Chiaretti S, Tavolaro S, Chia E M, et al. Characterization of ABL1 Expression in Adult T-Cell Acute Lymphoblastic Leukemia by Oligonucleotide Array Analysis. Haematologica/The Hematology Journal .2007; 92(5): 619-626.
  255. Chiaretti S, Vitale A, Cazzaniga G, et al. Clinico-Biological Features of 5202 Patients with Acute Lymphoblastic Leukemia Enrolled in the Italian AIEOP and GIMEMA Protocols and Stratified in Age Cohorts. Haematologica. 2013; 98(11): 1702-1710.
  256. Chillón M, Santamaría C, García-Sanz R, et al. Long FLT3 Internal Tandem Duplications and Reduced PML-RARa Expression at Diagnosis Characterize a High-Risk Subgroup of Acute Promyelocytic Leukemia Patients. Haematologica. 2010; 95: 745-751.
  257. Chou A, Fraser S, Toon CW, et al. A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma. Am J Surg Pathol. 2015;39:652-659.
  258. Chng WJ, Kuehl WM, Bergsage PL,  et al. Translocation t(4:14) retains prognostic significance even in the setting of high-risk molecular signature. Letter to the Editor. Leukemia. 2007; 22: 459-461.
  259. Cho M, Oweity T, Brandler T, et al. Distinguishing parathyroid and thyroid lesions on ultrasound-guided fine-needle aspiration: A correlation of clinical data, ancillary studies, and molecular analysis. Cancer Cytopathol. 2017;125: 674-82.
  260. Chou A, Fraser S, Toon CW, et al. A detailed clinicopathologic study of ALK-translocated papillary thyroid carcinoma. Am J Surg Pathol. 2015;39:652-659.
  261. Chua V, Lapadula D, Randolph C, et al. Dysregulated GPCR signaling and therapeutic options in uveal melanoma. Mol Cancer Res. 2017; 15(5): 501-506.
  262. Cibas ED, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. American Journal of Clinical Pathology. 2009; 132: 658-665.
  263. Cibas ES, Baloch ZW, Fellegara G, et al. A prospective assessment defining the limitations of thyroid nodule pathologic evaluation. Annals of Internal Medicine. 2013; 159(5): 325-32.
  264. Ciccarese C, Massari F, Blanca A, et al. Tp53 and its potential therapeutic role as a target in bladder cancer. Expert Opinion on Therapeutic Targets. 2017; 21(4): 401-414.
  265. Cingarlini S, Bonomi M, Corbo V, et al. Profiling mTOR pathway in neuroendocrine tumors. Target Oncol. 2012; 7: 183-188.
  266. Coates A, Winer E, Goldhirsch A, et al. Tailoring therapies – improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Annals of Oncology Advance Access. 2015; 26(8): 1-38.
  267. Cobain E, Hayes, D. Indications of Prognostic Gene Expression Profiling in Early Breast Cancer. Curr. Treat. Options in Oncol. 2015; 16(23): 1-14.
  268. Colamaio M, Calì G, Sarnataro D, et al. Let-7a down-regulation plays a role in thyroid neoplasias of follicular histotype affecting cell adhesion and migration through its ability to target the FXYD5 (Dysadherin) gene. Journal of Clinical Endocrinolology Metabolism. 2012; 97: E2168–E2178.
  269. Colamaio M, Borbone E, Russo L, et al. miR 191 down-regulation plays a role in thyroid follicular tumors through CDK6 targeting. Journal of Clinical Endocrinology Metabolism. 2011; 96: E1915–E1924.
  270. Collaud S, Tischler V, Atanassoff A, et al. Lung neuroendocrine tumors: correlation of ubiquitinylation and sumoylation with nucleo-cytosolic partitioning of PTEN. BMC Cancer. 2015 15(74): 1-10.
  271. College of American Pathologists (CAP), International Association for the Study of Lung Cancer (IASLC), and Association for Molecular Pathology (AMP). Molecular Testing Guideline for Selection of Lung Cancer Patients – Revision 2016 Draft Recommendations. Accessed July 17, 2017:https://www.iaslc.org/sites/ default/files/wysiwyg-assets/5-20160616 capiaslcamplungguideline-2016 draftrecommendations_ocpfinal.pdf
  272. Colombo C, Bolshakov S, Hajibashi S, et al. ‘Difficult to diagnose’ desmoid tumours: a potential role for CTNNB1 mutational analysis. Histopathology. 2011; 59: 336-340.
  273. Colombo C, Miceli R, Lazar AJ, et al. CTNNB1 45F Mutation is a molecular prognosticator of increased postoperative primary desmoid tumor recurrence: An independent, multicenter validation study. Cancer. 2013; 3696-3702.
  274. Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2009; 19(11): 1167-1214.
  275. Corbacioglu A, Scholl C, Schlenk R, et al. Prognostic Impact of Minimal Residual Disease in CBFB-MYH11-Positive Acute Myeloid Leukemia. Journal of Clinical Oncology. 2010; 28 (23): 3724-3729.
  276. Cordes I, Kluth M, Zygis D, et al. PTEN deletions are related to disease progression and unfavourable prognosis in early bladder cancer. Histopathology. 2013; 63: 670-677.
  277. Cordon-Cardo C, Wartinger D, Petrylak D, et al. Altered expression of the retinoblastoma gene product: Prognostic indicator in bladder cancer. J Natl Cancer Inst. 1992; 84(16): 1251-56.
  278. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. The Lancet. 2014; 384: 164-172.
  279. Costa C, Pereira S, Lima L, et al. Abnormal protein glycosylation and activated PI3K/Akt/mTOR pathway: Role in bladder cancer prognosis and targeted Therapeutics. PLoS One. 2015; 10(11): 1-19.
  280. Cros J, Hentic O, Rebours V, et al. MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors. Endocrine Related Cancer. 2016; 23(8): 625-633.
  281. Curtin J, Busam K, Pinkel D, Bastian B. Somatic Activation of KIT in Distinct Subtypes of Melanoma. Journal of Clinical Oncology. 2006; 24(26): 4340-4346.
  282. Damie R, Wasil T, Fais F, et al. Ig V Gene Mutation Status and CD38 Expression as Novel Prognostic Indicators in Chronic Lymphocytic Leukemia. Blood. 1999; 94 (6): 1840-1847.
  283. Daneshmand S, Bazargani S, Bivalacqua T, et. al. Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry. Urologic Oncology. https://doi.org/10.1016/j.urolonc.2018.04.013
  284. Daniilidou K, Frangou-Plemenou M, Grammatikakis J, et al. Prognostic significance and diagnostic value of PTEN and p53 expression in endometrial carcinoma. A retrospective clinicopathological and immunohistochemical study. J BUON. 2013; 18(1): 195-201.
  285. Daver N, Strati P, Jabbour E, et al. FLT3 Mutations in Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia. American Journal of Hematology. 2013; 88(1): 56-59.
  286. David, S, Patil, D, Alemozaffar M, et al. Urologist use of cystoscopy for patients presenting with hematuria in the United States. Urology. 2017; 100: 20-26.
  287. Davies L , Welch GH. Increasing Incidence of Thyroid Cancer in the United States, 1973-2002. JAMA. 2006; 295: 2164-2167.
  288. Davis R, Jones JS, Barocas DA, et al. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline, American Urological Association (AUA) guideline. 2012: 1-30.
  289. Dawson A, Bal S, McTavish B, et al. Inversion and Deletion of 16q22 Defined by Array CGH, FISH and RT-PCR in a Patient with AML. Cancer Genetics. 2011; 204(6): 344-347.
  290. Day F, Jorissen R, Lipton L, et al. PIK3CA and PTEN Gene and Exon Mutation-Specific Clinicopathologic and Molecular Associations in Colorectal Cancer. Clinical Cancer Research. 2013; 19(12): 3285-3296.
  291. Decaux O, Lode L, Magrangeas F, et al. Prediction of Survival in Multiple Myeloma Based on Gene Expression Profiles Reveals Cell Cycle and Chromosomal Instability Signatures in High-Risk Patients and Hyperdiploid Signatures in Low-Risk Patients: A Study of the Intergroupe Francophone du Myelome. Journal of Clinical Oncology. 2008; 26(24): 4798-4805.
  292. De Divitiis C, von Arx C, Grimaldi AM, et al. Metronomic temozolomide as second line treatment for metastatic poorly differentiated pancreatic neuroendocrine carcinoma. J Transl Med. 2016; 14(113): 1-12.
  293. Dekking E, van der Velden V, Varro R, et al. Flow Cytometric Immunobead Assay for Fast and Easy Detection of PML-RARA Fusion Proteins for the Diagnosis of Acute Promyelocytic Leukemia. Leukemia. 2012; 26: 1976-1985.
  294. Deng L, Chang D, Foshaug R, et al. Development and validation of a high-throughput mass spectrometry based urine metabolomic test for the detection of colonic adenomatous polyps. Metabolites. 2017; 7(32): 1-12. doi:10.3390/metabo7030032.
  295. Deng L, Fang H, Tso V, et al. Clinical validation of a novel urine-based metabolomic test for the detection of colonic polyps on Chinese population. Int J Colorectal Dis. 2017; 32:741-743.
  296. Derks J, Leblay N, Lantuejoul S, et al. New insights into the molecular characteristics of pulmonary carcinoids and large cell neuroendocrine carcinomas, and the impact on their clinical management. J Thorac Oncol. 2018: 1-15.
  297. Derks JL, Leblay N, Thunnissen E, et al. Molecular subtypes of pulmonary large-cell neuroendocrine carcinoma predict chemotherapy treatment outcome. Clin Cancer Res. 2018: 24(1): 33-42.
  298. De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11(8): 753-62.
  299. Dettmer MS, Perren A, Moch H, et al. MicroRNA profile of poorly differentiated thyroid carcinomas – new diagnostic and prognostic insights. Thyroid. 2013; 23(11): 1383-1389.
  300. Devaraj P, Foroni L, Kitra-Roussos V, et al. Detection of BCR-ABL and E2A-PBX1 Fusion Genes by RT-PCR in Acute Lymphoblastic Leukemia with Failed or Normal Cytogenetics. British Journal of Haematology. 1995: 349-355.
  301. Deverka P, Messner D, Dutta T. Center for Medical Technology Policy Effectiveness Guidance Document. Evaluation of Clinical Validity and Clinical Utility of Actionable Molecular Diagnostic Tests in Adult Oncology. Release Date: May 1, 2013.
  302. Di Narzo AF, Tejpar S, Rossi S, et al. Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data. J Natl Cancer Inst. 2014; 106(10): 1-8.
  303. Di Nicolantonio F, Martini M, Molinari F, et al. Wild-Type BRAF is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer. Journal of Clinical Oncology . 2008; 26 (35): 5705-5712.
  304. Di Noto R, Pardo C, Schiavone EM, et al. Stem Cell Factor Receptor (c-Kit, CD117) is Expressed on Blast Cells from most Immature Types of Acute Myeloid Malignancies but is also a Characteristic of a Subset of Acute Promyelocytic Leukaemia. British Journal of Haematology.  1996; 92(3): 562-564.
  305. Dos Santos LC, da Costa Ribeiro JC, Silva NP, et al. Cytogenetics, JAK2 and MPL mutations in polycythemia vera, primary myelofibrosis and essential thrombocythemia. Rev Bras Hematol Hemoter. 2011; 33(6): 417-24.
  306. Dos Santos MT, Mitne-Neto M, Miyashiro K, et al. Molecular genetic tests for JAK2V617F, Exon12_JAK2 and MPLW515K/L are highly informative in the evaluation of patients suspected to have BCR-ABL1-negative myeloproliferative neoplasms. J Clin Pathol. 2014; 67: 176-178.
  307. Dougherty M, Santi M, Brose M, et al. Activating Mutations in BRAF Characterize a Spectrum of Pediatric Low-Grade Gliomas. Neuro-Oncology.  2010; 12(7): 621-630.
  308. Downes, MR, Weening B, and van Rhijn VW, et al. Analysis of papillary urothelial carcinomas of the bladder with grade heterogeneity: supportive evidence for an early role of CDKN2A deletions in the FGFR3 pathway. Histopathology. 2017; 70: 281-289.
  309. Dowsett M, Cuzick J, Wale C, et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: A TransATAC study. Journal of Clinical Oncology. 2010; 28(11): 1829-1834.
  310. Dowsett M, Sestak I, Lopez-Knowles E, et al. Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy. J Clin Oncol. 2013; 31: 2783-2790. doi: 10.1200/JCO.2012.46.1558. Epub 2013 Jul 1.
  311. Duenas M, Martinez-Fernandez M, Garcia-Escudero R, et al. PIK3CA gene alterations in bladder cancer are frequent and associate with reduced recurrence in non-muscle invasive tumors. Molecular Carcinogenesis. 2015; 54: 566-576.
  312. Duick DS, Klopper JP, Diggans JC, et al. Test Results on the Endocrinologist–Patient Decision to Operate on Patients with Thyroid Nodules with Indeterminate Fine-Needle Aspiration Cytopathology. Thyroid. 2012; 22(10): 996-1001.
  313. Duployez N, Nibourel O, Marceau-Renaut A, et al. Minimal Residual Disease Monitoring in t(8;21) Acute Myeloid Leukemia Based on RUNX1-RUNX1T1 Fusion Quantification on Genomic DNA. American Journal of Hematology. 2014; 89(6): 1-6.
  314. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Report. Lancet. 2012; 379: 432-434.
  315. Ecke TH, Sach MD, Lenk SV, et al. TP53 gene mutations as an independent marker for urinary bladder cancer progression. International Journal of Molecular Medicine. 2008; 21: 655-661.
  316. Ecke TH, Schlechte HH, Hubsch A, et al. TP53 mutation in prostate needle biopsies-comparison with patients follow-up. Anticancer Res. 2007; 27: 4143-4148.
  317. Ecke TH, Schlechte HH, Schiemenz K, et al. TP53 gene mutations in prostate cancer progression. Anticancer Research. 2010; 30:1579-1586.
  318. Eisner R, Greiner R, Tso V, et al. A machine-learned predictor of colonic polyps based on urinary metabolomics. BioMed Research International. 2013; 303982: 1-11. http://dx.doi.org/10.1155/2013/303982
  319. Erickson LA. Papillary Thyroid Carcinoma. Atlas of Anatomic Pathology. 2014; 31-50.
  320. Espiritu SMG, Liu LY, Rubanova Y, et al. The evolutionary landscape of localized prostate cancers drives clinical aggression. Cell. 2018; 173: 1-11.
  321. Estep AL, Palmer C, McCormick F, Rauen KA. Mutation Analysis of BRAF, MEK1 and MEK2 in 15 Ovarian Cancer Cell Lines: Implications for Therapy. PLoS ONE. 2007; 2(12): e1279.
  322. Estrella JS, Broaddus RR, Mathews A, et al. Progesterone receptor and PTEN expression predict survival in patients with low- and intermediate-grade pancreatic neuroendocrine tumors. Arch Pathol Lab Med. 2014; 138: 1027-1036.
  323. Fahy K, Augustine L, Sanden M, et al. Clinicans’ Real World Perceptions of Pre-Nephrectomy Diagnostic Biopsy Performance as a Driver of Reduction in Unnecessary Surgeries in Renal Tumors. JKCVHL. 2015; 2(1): 1-14.
  324. Fang SH, Efron JE, Berho ME, et al. Dilemma of stage II colon cancer and decision making for adjuvant chemotherapy. J Am Coll Surg. 2014; 219(5): 1056-1069.
  325. Faquin W, Baloch ZW. Fine-Needle Aspiration of Follicular Patterned Lesions of the Thyroid: Diagnosis, Management, and Follow-Up According to National Cancer Institute (NCI) Recommendations. Diagnostic Cytopathology. 2010; 38: 731–739.
  326. Fekete M, Santiskulvong C, Eng C, Dorigo O. Effect of PI3K/Akt Pathway Inhibition-Mediated G1 Arrest on Chemosensitization in Ovarian Cancer Cells. Anticancer Research. 2012; 32: 445-452.
  327. FDA Labeling for ROMA Assay (Fujirebio R Diagnostics, Inc.)
  328. FDA 510(K) approval document. September 6, 2013
  329. Feng YZ, Shiozawa T, Miyamoto T, et al. BRAF Mutation in Endometrial Carcinoma and Hyperplasia: Correlation with KRAS and p53 Mutations and Mismatch Repair Protein Expression. Clin Cancer Res. 2005; 11: 6133-6138.
  330. Filipits M, Nielsen T, Rudas M, et al. The PAM50 Risk of Recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin Cancer Res. 2014; 20(5): 1-8.
  331. Fonseca R, Bergasagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma. Leukemia. 2009; 23: 2210-2221.
  332. Forconi F, Sozzi E, Cencini E, et al. Hairy Cell Leukemias with Unmutated IGHV Genes Define the Minor Subset Refractory to Single-Agent Cladribine and with more Aggressive Behavior. Blood. 2009; 114 (21): 4696-4702.
  333. Franc B, de la Salmoniere P, Lange F, et al. Interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma. Human Pathology. 2003; 34(11): 1092-100.
  334. Frates MC, Benson CB, Doubilet PM, et al. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. Journal of Clinical Endocrinology Metabolism. 2006; 91: 3411–3417.
  335. Fridman E, Dotan Z, Barshack I, et al. Accurate Molecular Classification Of Renal Tumors Using MicroRNA Expression. J Mol Diagn. 2010; 12(5): 687-96.
  336. Gale R, Green C, Allen C, et al. The Impact of FLT3 Internal Tandem Duplication Mutant Level, Number, Size, and Interaction with NPM1 Mutations in a Large Cohort of Young Adult Patients with Acute Myeloid Leukemia. Blood. 2008; 111 (5): 2776-2784.
  337. Gale R, Hills R, Pizzey A, et al. Relationship between FLT3 Mutation Status, Biologic Characteristics, and Response to Targeted Therapy in Acute Promyelocytic Leukemia. Blood. 2005; 106 (12): 3768-3776.
  338. Gallia G, Rand V, Siu I, et al. PIK3CA Gene Mutations in Pediatric and Adult Glioblastoma Multiforme. Mol Cancer Res. 2006; 4(10): 709-714.
  339. Gallucci MI, Guadagni F, Marzano R, et al. Status of the p53, p16, RB1, and HER-2 genes and chromosomes 3, 7, 9 and 17 in advanced bladder cancer: correlation with adjacent mucosa and pathological parameters. J Clin Pathol. 2005; 58: 367-71.
  340. Gao Q, Ye F, Xia X, et al. Correlation between PTEN Expression and PI3K/Akt Signal Pathway in Endometrial Carcinoma. Med Sci. 2009; 29(1): 59-63.
  341. Gao T, Mei Y, Sun H, et al. The association of phosphatase and tensin homolog (PTEN) deletion and prostate cancer risk: A meta-analysis. Biomedicine & Pharmacotherapy. 2016; 83:114-121.
  342. Gan X, Lin X, He R, et al. Prognostic and clinicopathological significance of downregulated p16 expression in patients with bladder cancer: A systematic review and meta-analysis. Dis Markers. 2016: 1-13.
  343. Garand R, Beldjord K, Cave H, et al. Flow Cytometry and IG/TCR Quantitative PCR for Minimal Residual Disease Quantitation in Acute Lymphoblastic Leukemia: a French Multicenter Prospective Study on Behalf of the FRALLE, EORTC and GRAALL. Leukemia. 2013; 27: 370-376.
  344. Garcia-Rostan G, Costa AM, Pereira-Castro I, et al. Mutation of the PIK3CA Gene in Anaplastic Thyroid Cancer. Cancer Res. 2005; 65: 10199-10207.
  345. Garcia-Saenz JA, Bermejo B, Estevez, G, et al. SEOM clinical guidelines in early-stage breast cancer 2015. Clinical Transl Oncol. 2015: 17(12); 939-945. DOI 10.1007/s12094-015-1427-3.
  346. Garcon I, Libura M, Delabesse E, et al. DEK-CAN Molecular Monitoring of Myeloid Malignancies Could Aid Therapeutic Stratification. Leukemia. 2005; 19: 1338-1344.
  347. Gazdar AF. Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 2009;28(Suppl 1): s24–s31.
  348. Geisler JP, Goodheart MJ, Sood AK, et al. Mismatch Repair Gene Expression Defects Contribute to Microsatellite Instability in Ovarian Carcinoma. Cancer. 2003; 98: 2199-2206.
  349. George J, Walter V, Peifer M, et al. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nat Commun. 2018; 9(1048): 1-13.
  350. Geybels MS, Fang M, Wright JL, et al. PTEN loss is associated with prostate cancer recurrence and alterations in tumor DNA methylation profiles. Oncotarget. 2017; 8(48): 84338-84348.
  351. Gharib H, Papini E, Paschke R, et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical Guide lines for Clinical Practice. Endocrinology Practice. 2010; 16(Suppl 1): 1-43.
  352. Gifford G, Paul J, Vasey PA, et al. The Acquisition of hMLH1 Methylation in Plasma DNA after Chemotherapy Predicts Poor Survival for Ovarian Cancer Patients. Clin Cancer Res. 2004; 10: 4420-4426.
  353. Giordano TJ, Kuick R, Thomas DG, et al. Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene. 2005; 24: 6646-6656.
  354. Glaser AP, Fantini D, Shilatifard A, et al. The evolving genomic landscape of urothelial carcinoma. Nature Reviews Urology. 2017; 14: 215-229.
  355. Gleeson FC, Voss JS, Kipp BR, et al. Assessment of pancreatic neuroendocrine tumor cytologic genotype diversity to guide personalized medicine using a custom gastroenteropancreatic next-generation sequencing panel. Oncotarget. 2017; 8(55): 93464-93475.
  356. Gnant M, Filipits M, Greil R, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Annals of Oncology. 2013; 00:1-7.
  357. Gnant M, Filipits M, Greil R, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Annals of Oncology. 2013 (Advance Access published December 16, 2013).
  358. Gnant M., Sestak I, Filipits M, et al. Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive early stage breast cancer treated with endocrine therapy: A combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and Intrinsic Subtype. Annals of Oncology. Advance Access May 1, 2015.
  359. Goebell PJ and Knowles MA. Bladder cancer or bladder cancers? Genetically distinct malignant conditions of the urothelium. Urol Oncol. 2010; 28: 409-428.
  360. Goldhirsch A, Winer E, Coates A, et al. Personalizing the treatment of women with early breast cancer: highlights of the St. Gallen International Expert Consensus of the Primary Therapy of Early Breast Cancer. Annals of Oncology. 2013; 24: 2206-2223.
  361. Goldman JW, Shi P, Reck M, et al. Treatment Rationale and Study Design for the JUNIPER Study: A Randomized Phase III Study of Abemaciclib With Best Supportive Care Versus Erlotinib With Best Supportive Care in Patients With Stage IV Non-Small-Cell Lung Cancer With a Detectable KRAS Mutation Whose Disease Has Progressed After Platinum-Based Chemotherapy. Clinical Lung Cancer. 2016; 17(1): 80-84.
  362. Gomez Saez JM. Diagnostic and Prognostic Markers in Differentiated Thyroid Cancer. Current Genomics. 2011; 12: 597-608.
  363. Goyal B, Duncavage EJ, Martinez D, et al. Next-generation sequencing of salivary high-grad neuroendocrine carcinomas identifies alterations in RB1 and the mTOR pathway. Experimental & Molecular Pathology. 2014; 97: 572-578.
  364. Goyle S, Maraveyas A. Chemotherapy for colorectal cancer. Dig Surg. 2005; 22: 401-414.
  365. Green C, Koo K, Hills R, et al. Prognostic Significance of CEBPA Mutations in a Large Cohort of Younger Adult Patients with Acute Myeloid Leukemia: Impact of Double CEBPA Mutations and the Interaction with FLT3 and NPM1 Mutations. Journal of Clinical Oncology. 2010; 28 (16): 2739-2747.
  366. Griewank KG, van de Nes J, Schilling B, et al. Genetic and clinic-pathologic analysis of metastatic uveal melanoma. Modern Pathology. 2014; 27: 175-183.
  367. Gruber JJ, Colevas AD. Differentiated Thyroid Cancer: Focus on Emerging Treatments for Radioactive Iodine-Refractory Patients. Oncologist. 2015; 20(2): 113-126. Epub 2015 Jan 23.
  368. Guikema J, deBoer C, Haralambieva E, et al. IGH Switch Breakpoints in Burkitt Lymphoma: Exclusive Involvement of Noncanonical Class Switch Recombination. Genes, Chromosomes & Cancer. 2006; 45(9): 808-819.
  369. Gunn S. Mohammed MS, Gorre ME,  et.al. Whole-genome scanning by array comparative genomic hybridization as a clinical tool for risk assessment in chronic lymphocytic leukemia. J. Mol. Diagn. 2008; 10:442-451.
  370. Haessler J, Shaughnessy JD, Zhan F, et al. Benefit of Complete Response in Multiple Myeloma Limited to High-Risk Subgroup Identified by Gene Expression Profiling. Clin Cancer Res. 2007; 13(23): 7073-7079.
  371. Haferlach C, Bacher U, Haferlach T, et al. The inv(3)(q21q26)/t(3;3)(q21;q26) is frequently accompanied by alterations of the RUNX1, KRAS and NRAS and NF1 genes and mediates adverse prognosis both in MDS and in AML: a study in 39 cases of MDS or AML. Leukemia. 2011; 25: 874-877.
  372. Hamada S, Futamura N, Ikuta K, et al. CTNNB1 S45F mutation predicts poor efficacy of meloxicam treatment for desmoid tumors: A pilot study. PLoS One. 2014 9(5): e96391, 1-6.
  373. Hamada S, Urakawa H, Kozawa E, et al: Nuclear expression of β-catenin predicts the efficacy of meloxicam treatment for patients with sporadic desmoid tumors. Tumour Biol. 2014; 35: 4561-4566.
  374. Hamaguchi H, Nagata K, Yamamoto K, et al. Establishment of a Novel Human Myeloid Leukaemia Cell Line (FKH-1) with T(6;9) (p23;q34) and the Expression of dek-can Chimaeric Transcript. British Journal of Haematology. 1998; 102(5): 1249-1256.
  375. Han C, Ma J, Zhao J, et al. EGFR Mutations, Gene Amplification, and Protein Expression and KRAS Mutations in Primary and Metastatic Tumors of Nonsmall Cell Lung Cancers and Their Clinical Implications: A Meta-Analysis. Cancer Investigation. 2011; 29: 626-634.
  376. Han X, Ji Y, Zhao J, et al. Expression of PTEN and mTOR in pancreatic neuroendocrine tumors. Tumour Biol. 2013; 34: 2871-2879.
  377. Handolias D, Hamilton AL, Salemi R, et al. Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT. British Journal of Cancer. 2010; 102: 1219-1223.
  378. Hanna N, Johnson D, Temin S, et al. Systemic therapy for stage IV non–small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update. Journal of Clinical Oncology. 2017;35:3484-3515.
  379. Hari PN, Zhang MJ, Roy V, et al. Is the international Staging System superior to the Durie-Salmon staging system? A comparison in multiple myeloma patients undergoing autologous transplant. Leukemia. 2009: 23(8); 1528-34. Doi: 10.1038/leu.2009.61
  380. Hayette S, Tigaud I, Thomas X, et al. Identification of a Rare e6a2 BCR-ABL Fusion Gene During the Disease progression of Chronic Myelomonocytic Leukemia: A Case Report. Leukemia. 2004; 18: 1735-1736.
  381. He H, Jazdzewski K, Li W, et al. The role of microRNA genes in papillary thyroid carcinoma. Proceedings of the National Academy of Science. 2005; 102: 19075–19080.
  382. He M, Breese V, Hang S, Zhang C, Xiong J, Jackson C. BRAF V600E Mutations in Endometrial Adenocarcinoma. Diagn Mol Pathol. 2013; 22(1): 35-40.
  383. He Y, Van't Veer LJ, Mikolajewska-Hanclich I, et al. PIK3CA mutations predict local recurrences in rectal cancer patients. Clin Cancer Res. 2009; 15(22): 6956-62.
  384. Hegedus L. Clinical practice. The thyroid nodule. New England Journal of Medicine. 2004; 351: 1764–1771.
  385. Helmle KE, Otto CJ, Constantinescu G, Honore LH, Andrew SE. Variable MLH1 promoter methylation patterns in endometrial carcinomas of endometrioid subtype lacking DNA mismatch repair. Int J Gynecol Cancer. 2005; 15: 1089-1096.
  386. Herandez-Aya L, Gonzalez-Angulo A. Adjuvant Systemic Therapies in Breast Cancer. Surg Clin North Am. 2013; 93(2): 473-491.
  387. Herling M, Patel K, Teitell M, et al. High TCL1 expression and intact T-cell receptor signaling define a hyperproliferative subset of T-cell prolymphocytic leukemia. Blood. 2008; 111: 328-337.
  388. Hershman J, Lyko A. Follicular Thyroid Carcinoma. Endocrine Updates. 2012; 32: 155-169.
  389. Holmfeldt L, Wei L, Diaz-Flores E, et al. The Genomic Landscape of Hypodiploid Acute Lymphoblastic Leukemia. Nature Genetics. 2013; 45(3): 242-252.
  390. Horny H, Lange K, Sotlar K, et. al. Increase of Bone Marrow Lymphocytes in Systemic Mastocytosis: Reactive Lymphocytosis or Malignant Lymphoma? Immunohistochemical and Molecular Findings on Routinely Processed bone Marrow Biopsy Specimens. J Clin Pathol. 2003; 56: 575-578.
  391. Hose D, Reme T, Hielscher T, et al. Proliferation is a central independent prognostic factor and target for personalized and risk adapted treatment in multiple myeloma. Haematologica. Sept 2010.
  392. Hou H, Kuo Y, Liu C, et al. DNMT3A Mutations in Acute Myeloid Leukemia: Stability during Disease Evolution and Clinical Implications. Blood. 2012; 119(2): 559-568.
  393. Hughes T, Branford S. Molecular Monitoring of BCR-ABL as a Guide to Clinical Management in Chronic Myeloid Leukaemia. Blood Rev. 2006; 20 (1): 29-41.
  394. Hummel J, Carmen Frias Kletecka M, Sanks J, et al. Concomitant BCR-ABL1 Translocation and JAK2V617F Mutation in Three Patients with Myeloproliferative Neoplasms. Diagn Mol Pathol. 2012; 21: 176-183.
  395. Hundahl SA, Cady B, Cunningham MP, et al. Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the United States during 1996. U.S. and German Thyroid Cancer Study Group. An American College of Surgeons Commission on Cancer Patient Care Evaluation study. Cancer. 2000; 89(1): 202-17.
  396. Huss S, Nehles J, Binot E, Et al. β catenin (CTNNB1) mutations and clinciopathological features of mesenteric desmoid-type fibromatosis. Histopathology. 2013; 62: 294-304.
  397. Hussain M, Daignault-Newtown S, Twardowski PW, et al. Targeting androgen receptor and DNA repair in metastatic castration-resistant prostate cancer: Results from NCI 9012. J Clin Oncol. 2018; 36(10): 991-999.
  398. Hyman DM, Puzanov I, Bubbiah V, et al. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N.Eng J Med. 2015; 373(8): 726-736.
  399. Hyman D, Smyth L, Donoghue M, et al. AKT Inhibition in Solid Tumors with AKT1 Mutations. Journal of Clinical Oncology. 2017; 35(20); 2251-2259.
  400. Ida C, Lambert S, Fausto J, et al. BRAF Alterations are Frequent in Cerebellar Low-Grade Astrocytomas with Diffuse Growth Pattern. J Neuropathol Exp Neurol. 2012; 71(7): 631-639.
  401. Ikezoe T, Kojima S, Furihata M, et al. Expression of p-JAK2 Predicts Clinical Outcome and is a Potential Molecular Target of Acute Myelogenous Leukemia. International Journal of Cancer. 2011; 129(10): 2512-2521.
  402. Iorio MV, Ferracin M, Liu CG, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Research. 2005; 65: 7065–7070.
  403. Ishida H, Kasajima A, Kamei T, et al. SOX2 and Rb1 in esophageal small-cell carcinoma: their possible involvement in pathogenesis. Modern Pathology. 2017; 30: 660-671.
  404. Itonaga H, Tsushima H, Imanishi D, et al. Molecular Analysis of the BCR-ABL1 Kinase Domain in Chronic-Phase Chronic Myelogenous Leukemia Treated with Tyrosine Kinase Inhibitors in Practice: Study by the Nagasaki CML Study Group. Leukemia Research. 2014;38 (1): 76-83.
  405. Iyer G, Al-Ahmadie H, Schultz N, et al. Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol. 2013; 31(25): 3133-3140.
  406. Jain P, Kantarjian H, Patel K, et al. Mutated NPM1 in Patients with Acute Myeloid Leukemia in Remission and Relapse. Leukemia & Lymphoma 2013: 1-8.
  407. Jakob JA, Bassett RL Jr, Ng CS, et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer. 2012; 118(16): 4014-23.
  408. Jamasphishvili T, Berman DM, Ross AE, et al. Clinical implications of PTEN loss in prostate cancer. Nature Reviews Urology. 2018; 15: 222-234.
  409. Jeuken J, Sijben A, Alenda C, et al. Robust Detection of EGFR Copy Number Changes and EGFR Variant III: Technical Aspects and Relevance for Glioma Diagnostics. Brain Pathology. 2009; 19: 661-671.
  410. Ji JH, Oh YL, Hong M, et al. Identification of driving ALK fusion genes and genomic landscape of medullary thyroid cancer. PLoS Genet. 2015;11(8):e1005467. https:// doi.org/10.1371/journal.pgen.1005467
  411. Jiang Y, Gao B, Zhang X, et al. Prevention and treatment of recurrent laryngeal nerve injury in thyroid surgery. International Journal of Clinical Experience in Medicine. 2014; 7(1): 101-7.
  412. Jiao Y, Shi C, Edil BH, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science. 2011; 331(6021): 1199-1203.
  413. Jin S, Chang IH, Kim JW, et al. Identification of downstream genes of the mTOR pathway that predict recurrence and progression in non-muscle invasive high-grade urothelial carcinoma of the bladder. J Korean Med Sci. 2017; 32:1327-1336.
  414. Jo VY, Stelow EB, Dustin SM, et al. Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda system for reporting thyroid cytopathology. American Journal of Clinical Pathology. 2010; 134: 450–6.
  415. Jocham D, Stepp H, Waidelich R. Photodynamic diagnosis in urology: State-of-the-art. European Urology. 2008; 53: 1138-1150.
  416. Joseph RW, Sullivan RJ, Harrell R, et al. Correlation of NRAS Mutations With Clinical Response to High-dose IL-2 in Patients With Advanced Melanoma. Journal of Immunotherapy. 2012; 35: 66-72.
  417. Jug R, Datto M, Jiang X. Molecular testing for indeterminate thyroid nodules: Performance of the afirma gene expression classifier and ThyroSeq panel. Cancer Cytopathol. 2018. DOI: 10.1002/cncy.21993, wileyonlinelibrary.com.
  418. Kadia T, Kantarjian H, Kornblau S, et al. Clinical and Proteomic Characterization of Acute Myeloid Leukemia with Mutated RAS. Cancer. 2012; 118(22): 5550-5559.
  419. Kaeferstein A, Krug U, Tiesmeier J, et al. The emergence of a C/EBPα mutation in the clonal evolution of MDS towards secondary AML. Leukemia. 2003; 17: 343-349.
  420. Kaneki E, Oda Y, Ohishi Y, et al. Frequent Microsatellite Instability in Synchronous Ovarian and Endometrial Adenocarcinoma and Its Usefulness for Differential Diagnosis. Human Pathology. 2004; 35: 1484-1493.
  421. Kavalieris L, O'Sullivan P, Frampton C, et al. Performance Characteristics of a Multigene Urine Biomarker Test for Monitoring for Recurrent Urothelial Carcinoma in a Multicenter Study.  The Journal of Urology. (2017), DOI 10.1016/j.juro.2016.12.010
  422. Kavalieris L, O'Sullivan PJ, Suttie JM, et al. A segregation index combining phenotypic (clinical Characteristics) and genotypic (gene expression) biomarkers from a urine sample to triage out patients presenting with hematuria who have a low probability of urothelial carcinoma. BMC Urology. 2015; 15: 23. DOI 10.1186/s12894-015-0018-5
  423. Keedy VL, Temin S, Somerfield MR, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients With Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011; 29: 2121-2127.
  424. Kelemen K, Kovacsovics T, Braziel R, et al. RAS Mutations in Therapy-Related Acute Myeloid Leukemia after Successful Treatment of Acute Promyelocytic Leukemia. Leukemia & Lymphoma. 2012; 53(5): 999-1002.
  425. Kennedy RD, Bylesjo M, Kerr P, et al. Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue. J Clin Oncol. 2011; 29(35): 4620-4626.
  426. Keutgen XM, Filicori F, Crowley MJ, et al. A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. Clinical Cancer Research. 2012; 18:2032-2038.
  427. Kilon A, Noel P, Akin C, et al. Elevated Serum Tryptase Levels Identify a Subset of Patients with a Myeloproliferative Variant of Idiopathic Hypereosinophilic Syndrome Associated with Tissue Fibrosis, Poor Prognosis, and Imatinib Responsiveness. Blood. 2003; 101(12): 4660-4666.
  428. Kim I, Kim H, Choung H, et al. PML/RARA Rearrangement Associated with a t(15;19;17) in a Case of Acute Myeloid Leukemia with Abundant Myelocytes with Salmon-pink Cytoplasm. Cancer Genetics and Cytogenetics. 2006; 169(1): 81-82.
  429. Kim PH, Cha EK, Sfakianos JP, et al. Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder. European Urology. 2015; 67: 198-201.
  430. Kim TH, Park YJ, Lim JA, et al. The Association of the BRAFV600E Mutation With Prognostic Factors and Poor Clinical Outcome in Papillary Thyroid Cancer: A Meta-Analysis. Cancer. 2012; 118: 1764-73.
  431. Kitano M, Rahbari R, Patterson EE, et al. Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples. Thyroid. 2012; 22: 285-291.
  432. Kiyoi H, Naoe T, Nakano Y, et al. Prognostic Implication of FLT3 and N-RAS Gene Mutations in Acute Myeloid Leukemia. Blood. 1999; 93(9): 3074-3080.
  433. Kluth M, Harasimowicz S, Burkhardt L, et al. Clinical significance of different types of p53 gene alteration in surgically treated prostate cancer. Int J Cancer. 2014; 135:1369-1380.
  434. Kohlmann A, Grossmann V, Klein H, et al. Next-Generation Sequencing Technology Reveals a Characteristic pattern of Molecular Mutations in 72.8% of Chronic Myelomonocytic Leukemia by Detecting Frequent Alterations in TET2, CBL, RAS, and RUNX1. Journal of Clinical Oncology. 2010; 28 (24): 3858-3865.
  435. Kolasa IK, Rembiszewska A, Janiec-Jankowska A, et al. PTEN mutation, expression and LOH at its locus in ovarian carcinomas. Relation to TP53, K-RAS and BRCA1 mutations. Gynecologic Oncology. 2006; 103: 692-697.
  436. Kolquist K, Schultz RA, Furrow A,  et.al. Microarray-based comparative genomic hybridization of cancer targets reveals novel recurrent genetic aberrations in the myelodysplastic syndromes. Cancer Genet. 2011; 204: 603-628.
  437. Kompier LC, Lurkin I, van der Aa MN, et al. FGFR3 HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy. PLoS One. 2010; 5(11) e13821: 1-13.
  438. Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nature Reviews Cancer. 2006; 6(4): 292-306.
  439. Konukiewitz B, Schlitter AM, Jesinghaus M, et al. Somatostatin receptor expression related to TP53 and RB1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with a Ki67-index above 20%. Modern Pathology. 2017; 30: 587-598.
  440. Kook H, Risitano An, Zeng W, et al. Changes in T-cell Receptor VB Repertoire in Aplastic Anemia: Effects of Different Immunosuppressive Regimens. Blood. 2002; 99 (10): 3668-3675.
  441. Korkolopoulu P, Levidou G, Trigka EA, et al. A comprehensive immunohistochemical and molecular approach to the PI3K/AKT/mTOR (phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene/mammalian target of rapamycin) pathway in bladder urothelial carcinoma. BJU Int. 2012; 110: E1237-1248.
  442. Kosmider O, Gelsi-Boyer V, Slama L, et al. Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms. Leukemia. 2010; 24: 1094-1096.
  443. Krakstad C, Birkeland E, Seidel D, et al. High-Throughput Mutation Profiling of Primary and Metastatic Endometrial Cancers Identifies KRAS, FGFR2 and PIK3CA to Be Frequently Mutated. PLoS ONE. 2012; 7(12): e52795.
  444. Krausch M, Raffel A, Anlauf M, Loss of PTEN Expression in neuroendocrine pancreatic tumors. Horm Metab Res. 2011; 43: 865-871
  445. Kristensen T, Vestergaard H, Bindslev-Jensen C, et al. Sensitive KIT D816V Mutation Analysis of Blood as a Diagnostic Test in Mastocytosis. American Journal of Hematology. 2014: 1-6.
  446. Kulac I, Arslankoz S, Netto GJ, et al. Reduced immunohistochemical PTEN staining is associated with higher progression rate and recurrence episodes in non-invasive low-grad papillary urothelial carcinoma of the bladder. Virchows Arch. 2018. https://doi.org/10.1007/s00428-018-2302-8
  447. Kulke MH, Hornick JL, Frauenhoffer C, et al. 06-methylguanine DNA methyltransferase deficiency and response to Temozolomid-based therapy in patients with neuroendocrine tumors. Clin Cancer Res. 2009; 15(1): 338-345.
  448. Lai A, Kharbanda S, Pope W, et al. Evidence for Sequenced Molecular Evolution of IDH1 Mutant Glioblastoma from a Distinct Cell of Origin. Journal of Clinical Oncology. 2011; 29 (34): 4482-4490.
  449. Land SR, Kopec JA, Cecchini RS, et al. Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07. J Clin Oncol. 2007; 25(16): 2205-2211.
  450. Laurent-Puig P, Gilles A, Buc M, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol. 2009; 27(35): 5924-5930.
  451. Lazar AJ, Tuvin D, Hajibashi S, et al. Specific mutations in the β-Catenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol. 2008; 173(5): 1518-27.
  452. Lazaris AC, Zarogiannos A, Kavantzas N, et al. MLH1 Mismatch Repair Gene Product is Associated with Apoptotic Potential of Urothelial Bladder Carcinomas. Anticancer Research. 2006; 26: 1535-1542.
  453. Lee H, Choi SK, and Ro JY. Overexpression of DJ-1 and HSP90a, and loss of PTEN associated with invasive urothelial carcinoma of urinary bladder: Possible prognostic markers. Oncology Letters. 2012; 3: 507-512.
  454. Lee L, How J, Tabah RJ, et al. Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology. Journal of Clinical Endocrinology and Metabolism. 2014; 99(8): 2674-82.
  455. Lee SH, Kim JE, Jang HS, et al. Genetic alterations among Korean melanoma patients showing tumor heterogeneity: A comparison between primary tumors and corresponding metastatic lesions. Accepted Article. Cancer Research and Treatment. 2018: 1-29. Doi: 10.4143/crt.2017.535
  456. Le Guellec S, Soubeyran I, Rochaix P, et al. CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: a study of 260 desmoid tumors and 191 potential morphologic mimic. Modern Pathology. 2012; 25: 1551.-58.
  457. Leventaki V, Rodic V, Tripp S, et al. TP53 Pathway Analysis in Paediatric Burkitt Lymphoma Reveals Increased MDM4 Expression as the only TP53 Pathway Abnormality Detected in a Subset of Cases. British Journal of Haematology. 2012; 158(6): 763-771.
  458. Levine Rl, Gilliland DG. JAK-2 Mutations and their Relevance to Myeloproliferative Disease. Curr Opin Hematol. 2007; 14(1): 43-7.
  459. Ley T, Ding L, Walter M, et al. DNMT3A Mutations in Acute Myeloid Leukemia. The New England Journal of Medicine. 2010; 363(25): 2424-2433.
  460. Li AFY, Tsay SH, Liang WY, et al. Clinical Significance of p16INK4A and p53 overexpression in endocrine tumors of the gastrointestinal tract. Am J Clin Pathol. 2006; 126: 856.865.
  461. Li B, Liu S, Niu Y, et al. Altered Expression of the TCR Signaling Related Genes CD3 and FC?Rl? in Patients with Aplastic Anemia. Journal of Hematology & Oncology. 2012; 5: 1-7.
  462. Li H, Robinson KA, Anton B, et al. Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules. Journal of Clinical Endocrinology and Metabolism. 2011; 96(11): E1719-26.
  463. Liao X, Morikawa T, Lochhead P, et al. Prognostic Role of PIK3CA Mutation in Colorectal Cancer: Cohort Study and Literature Review. Clinical Cancer Research. 2012; 18(8): 2257-2268.
  464. Lim S, Koh MJ, Jeong HJ, et al. Fibroblast growth factor receptor 1 overexpression Is associated with poor survival in patients with resected muscle invasive urothelial carcinoma. Yonsei Med J. 2016; 57(4):831-839.
  465. Lin C, Lai Y, Lin T, et al. Clinicopathologic Features and Prognostic Analysis of MSI-High Colon Cancer. Int J Colorectal Dis. 2012; 27(3): 277-286.
  466. Lin J, Yao D-m, Qian J, et al. IDH1 and IDH2 mutation analysis in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol. 2012; 91: 519-525.
  467. Lin J, Yao D-m, Qian J, et al. Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome. PLoS ONE. 2011; 6(10): e26906.
  468. Lin VC, Huang CY, Lee YC, et al. Genetic variations in TP53 binding sites are predictors of clinical outcomes in prostate cancer patients. Arch Toxicol. 2014; 88: 901-911.
  469. Lindeman NI, Cagle PT, Aisner DL, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: Guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. The Journal of Molecular Diagnostics. 2018; 20(2): 129-159.
  470. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med. 2013; 137(6): 828-860.
  471. Liu L, Wang J, Li X, et al. miR-204-5p suppresses cell proliferation by inhibiting IGFBP5 in papillary thyroid carcinoma. Biochemistry Biosphysics Research Community. 2015; 457(4): 621-6.
  472. Liu W, X Tan, Luo X, et al. Prognostic Significance of Tet Methylcytosine Dioxygenase 2 (TET2) Gene Mutations in Adult Patients with Acute Myeloid Leukemia: a Meta-analysis. Leukemia & Lymphoma. 2014; 55: 1-8.
  473. Liu X, Jia Y, Stoopler MB, et al. Next-Generation Sequencing of Pulmonary Sarcomatoid Carcinoma Reveals High Frequency of Actionable MET Gene Mutations. J Clin Oncol. 2016; 34(8): 794-802.
  474. Liu Y, Yanbin S, Wenli M, et al. Decreased MicroRNA-30a Levels are Associated with Enhanced ABL1 and BCR-ABL1 Expression in Chronic Myeloid Leukemia. Leukemia Research. 2013; 37(3): 349-356.
  475. Livhits MJ, Kuo EJ, Leung AM, et al. Gene expression classifier versus targeted next-generation sequencing in the management of indeterminate thyroid nodules. JCEM. 2018. Advance online publication. DOI: 10.1210/jc.2017-02754/4951503
  476. Lloyd RV, Erickson LA, Casey MB, et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. American Journal of Surgical Pathology. 2004; 28(10):1336-40.
  477. Lokhandwala T, Bittoni MA, Dann RA, et al. Costs of Diagnostic Assessment for Lung Cancer: A Medicare Claims Analysis. Clin Lung Cancer. 2017;18(1): e27-e34.
  478. Lokman U, Erickson AM, Vasarainen H, et al. PTEN loss but not ERG expression in diagnostic biopsies Is associated with increased risk of progression and adverse surgical findings in men with prostate cancer on active surveillance. European Urology Focus. 2017: 1-7.
  479. Lopez-Knowles E, Hernandez S, Malats N, et al. PIK3CA mutations are an early genetic alteration associated with FGR3 mutations in superficial papillary bladder tumors. Cancer Res. 2006; 66(15): 7401-4.
  480. Lorenzo F, Nishii K, Monma F, et al. Mutational analysis of the KIT gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia. Leukemia Research. 2006; 30: 1235-1239.
  481. Lotan Y, O'Sullivan P, Raman JD, et al. Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma. Urologic Oncology: Seminars and Original Investigations. 2017; http://dx.doi.org/10.1016/j.urolonc.2017.03.008
  482. Lough T, Luo Q, Luxmanan C, et al. Clinical utility of a non-invasive urine test for risk assessing patients with no obvious benign cause of hematuria: a physician-patient real world data analysis. BMC Urology 2018; 18(18): 1-9.
  483. Lough T, Luo Q, O’Sullivan P, et al. Clinical utility of Cxbladder monitor for patients with a history of urothelial carcinoma: A physician-patient real-world clinical data analysis. Oncol Ther. https://doi.org/10.1007/s40487-018-0059-5.
  484. Lorenzo F, Nishii K, Monma F, et al. Mutational analysis of the KIT gene in myelodysplastic syndrome (MDS) and MDS-derived leukemia. Leukemia Research. 2006; 30: 1235-1239.
  485. Lotan Y, O'Sullivan P, Raman JD, et al. Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma. Urologic Oncology: Seminars and Original Investigations. 2017; http://dx.doi.org/10.1016/j.urolonc.2017.03.008
  486. Louie CY, Concepcion W, Park JK, et al. Hepatoblastoma arising in a pigmented β-catenin-activated hepatocellular adenoma: Case report and review of the literature. Am J Surg Pathol. 2016; 40(7): 998-1003.
  487. Lu J, Getz G, Miska EA. MicroRNA expression profiles classify human cancers. Nature. 2005; 435: 834–838.
  488. Lubitz CC, Kong CY, McMahon PM, et al. Annual Financial Impact of Well-Differentiated Thyroid Cancer Care in the United States. Cancer. 2014; 120: 1345–52.
  489. Ludovini V, Bianconi F, Pistola L, et al. Phosphoinositide-3-kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer. J Thoracic Oncol. 2011; 6(4): 707-715.
  490. Lundin C, Hjorth L, Behrendtz M, et al. Submicroscopic Genomic Imbalances in Burkitt Lymphomas/Leukemias: Association with Age and Further Evidence that 8q24/MYC Translocations are not Sufficient for Leukemogenesis. Genes, Chromosomes & Cancer. 2013; 52: 370-377.
  491. Mack PC, Chi SG, Meyers FJ, et al. Increased RB1 abnormalities in human primary prostate cancer following combined androgen blockade. Prostate. 1998; 34: 145-151.
  492. Mackay HJ, Gallinger S, Tsao MS, et al. Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: Results from studies of the NCIC Clinical Trials Group (NCIC CTG). European Journal of Cancer. 2010; 46: 1365-1373.
  493. Malekzadeh K, Sobti RC, Nikbakht M, et al. Methylation patterns of Rb1 and Casp-8 promoters and their impact on their expression in bladder cancer. Cancer Invest. 2009; 27: 70-80.
  494. Mansour WY, Tennstedt P, Volquardsen J, et al. Loss of PTEN-assisted G2/M checkpoint impedes homologous recombination repair and enhances radio-curability and PARP inhibitor treatment response in prostate cancer. Scientific Reports. 2018; 8(3947): 1-12.
  495. Marcucci G, Maharry K, Wu Y, et al. IDH1 and IDH2 Gene Mutations Identify Novel Molecular Subsets within De Novo Cytogenetically Normal Acute Myeloid Leukemia: a Cancer and Leukemia Group B Study. Journal of Clinical Oncology. 2010; 28 (14): 2348-2355.
  496. Margolskee E, Bao F, de Gonzalez AK, et al. Hepatocellular adenoma classification: a comparative evaluation of immunohistochemistry and targeted mutational analysis. Diagn Pathol. 2016; 11(27): 1-10.
  497. Martin M, Gonzalez-Rivera M, Morales S, et al. Prospective study of the impact of Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer. Current Medical Research & Opinion. 2015; 1-9.
  498. Mazzaferri EL, de los Santos ET, Rofagha-Keyhani S. Solitary thyroid nodule: diagnosis and management. Medical Clinics of North America. 1988; 72: 1177–1211.
  499. McHenry CR, Slusarczyk SJ. Hypothyroidisim following hemithyroidectomy: Incidence, risk factors, and management. Surgery. 2000; 128:994-8.
  500. McIver B, Castro MR, Morris JC, et al. An Independent Study of a Gene Expression Classifier (Afirma) in the Evaluation of Cytologically Indeterminate Thyroid Nodules. Journal of Clinical Endocrinology and Metabolism. 2014; 99: 4069–4077.
  501. Meeks JJ, Carneior BA, Pai SG, et al. Genomic Characterization of high-risk non-muscle invasive bladder cancer. Oncotarget. 2016; 7(46): 75176-75184.
  502. Mehta V, Nikiforov YE, Ferris RL. Use of molecular biomarkers in FNA specimens to personalize treatment for thyroid surgery. Head & Neck. 2013; 35(10):1499-506.
  503. Metzeler K, Maharry K, Radmacher M, et al. TET2 Mutations Improve the New European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study. Journal of Clinical Oncology. 2011; 29(10): 1373-1380.
  504. Mian C, Pennelli G, Fassan M, et al. MicroRNA profiles in familial and sporadic medullary thyroid carcinoma: preliminary relationships with RET status and outcome. Thyroid. 2012; 22: 890–896.
  505. Michael MZ, O’ Connor SM, van Holst Pellekaan NG, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia. Molecular Cancer Research. 2003; 1:882 – 891.
  506. Mikami T, Nemoto Y, Numata Y, et al. Small Gastrointestinal Stromal Tumor in the Stomach: Identification of Precursor for Clinical Gastrointestinal Stromal Tumor Using C-KIT and A-Smooth Muscle Actin Expression. Human Pathology. 2013; 44(12): 2628-2635.
  507. Missiaglia E. Dalai I, Barbi S, et al. Pancreatic endocrine tumors: Expression profiling evidences a role for AKT-mTor pathway. J Clin Oncol. 2010; 28(2): 245-255
  508. Mitomo S, Maesawa C, Ogasawara S, et al. Downregulation of miR 138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines. Cancer Science. 2008; 99: 280–286.
  509. Miyoshi T, Umemura S, Matsumura Y, et al. Genomic profiling of large-cell neuroendocrine carcinoma of the lung. Clin Cancer Res. 2017; 23(3): 757-765.
  510. Mundhenk J, Hennenlotter J, Zug L, et al. Evidence for PETN-independent Akt activation and Akt-independent p27Kip 1 expression in advanced bladder cancer. Oncology Letters. 2011; 2: 1089-1093.
  511. Myers MB, McKim KL, Parsons BL. A Subset of Papillary Thyroid Carcinomas Contain KRAS Mutant Subpopulations at Levels Above Normal Thyroid. Molecular Carcinogenesis. 2014; 53: 159-167.
  512. Nagaiah G, Hossain A, Mooney CJ, et al. Anaplastic Thyroid Cancer: A Review of Epidemiology, Pathogenesis, and Treatment. Journal of Oncology. 2011. Article ID 542358, 13 pages, 2011.
  513. Nair B, Shaughnessy Jr JD, Zhou Y, et al. Gene expression profiling of plasma cells at myeloma relapse from tandem transplantation trial Total Therapy 2 predicts subsequent survival. Blood. 2009; 113: 6572-6575.
  514. National Cancer Institute. SEER Stat Fact Sheets: Thyroid Cancer. Bethesda, MD. Available at: http://seer.cancer.gov/statfacts/html/thyro.html. Published April 2014. Accessed on February 12, 2015
  515. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Bladder Cancer, Version 2.2017 - Feb 15, 2017. NCCN.org.
  516. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer, Version 2.2018 - March 14, 2018. NCCN.org
  517. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Breast Cancer, Version 2. 2016.
  518. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Thyroid Carcinoma. Version 1.2013.
  519. National Comprehensive Cancer Network (NCCN). NCCN Guidelines Version 5.2018, Bladder Cancer. June 27, 2018.
  520. National Comprehensive Cancer Network (NCCN). Non-Hodgkin's Lymphoma (NHL) (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf (Page CSLL-1, CSLL-A). Accessed April 25, 2014.
  521. National Comprehensive Cancer Network (NCCN). Chronic Myelogenous Leukemia (CML) (Version 3.2014). http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf (Page CML-1, CML-2, CML-3, CML-4, CML-5, CML-A, CML-6, CML-8). Accessed April 25, 2014.
  522. National Comprehensive Cancer Network (NCCN). Chronic Myelogenous Leukemia (CML) (Version 3.2014). http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf (Page CML-J, CML-2, CML-3, CML-4, CML-5, CML-A, CML-6). Accessed April 25, 2014.
  523. National Comprehensive Cancer Network (NCCN). Non-Hodgkin's Lymphoma (NHL) (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf (Page FOLL-1). Accessed April 25, 2014.
  524. National Comprehensive Cancer Network (NCCN). Non-Hodgkin's Lymphoma (NHL) (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf (Page HCL-1). Accessed April 25, 2014.
  525. National Comprehensive Cancer Network (NCCN). Non-Hodgkin's Lymphoma (NHL) (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf (Page MANT-1). Accessed April 25, 2014.
  526. National Comprehensive Cancer Network (NCCN). Acute Myeloid Leukemia (AML) (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf (Page AML-A). Accessed April 25, 2014.
  527. National Comprehensive Cancer Network (NCCN). Acute Myeloid Leukemia (AML) (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf (Page AML-1, AML-10, AML-A). Accessed April 25, 2014.
  528. National Comprehensive Cancer Network (NCCN). Acute Lymphoblastic Leukemia (Version 3.2013). http://www.nccn.org/professionals/physician_gls/pdf/all.pdf (Page ALL-1). Accessed April 25, 2014.
  529. National Comprehensive Cancer Network (NCCN). Acute Lymphoblastic Leukemia (Version 3.2013). http://www.nccn.org/professionals/physician_gls/pdf/all.pdf (Page ALL-D 3 of 4, ALL-7). Accessed April 25, 2014.
  530. National Comprehensive Cancer Network (NCCN). Acute Myeloid Leukemia (AML) (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/aml.pdf (Page AML-2, AML-A, AML-5, AML-6). Accessed April 25, 2014.
  531. National Comprehensive Cancer Network (NCCN). Central Nervous System Cancers (Version 1.2014). http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. (Page GLIO-3). Accessed April 25, 2014.
  532. National Comprehensive Cancer Network (NCCN). Central Nervous System Cancers (Version 1.2014). http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. (Page ASTR-1). Accessed April 25, 2014.
  533. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer (Version 2.2014). Accessed 12/12/2013. NCCN.org
  534. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Small Cell Lung Cancer (Version 2.2014). Accessed 12/12/2013. NCCN.org
  535. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Melanoma (Version 2.2014). Accessed 12/12/2013. NCCN.org
  536. National Comprehensive Cancer Network (NCCN). Colon Cancer (Version 3.2014). http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf (Page COL-A 4 of 5, COL-5, COL-9). Accessed April 25, 2014.
  537. National Comprehensive Cancer Network (NCCN). Colon Cancer (Version 3.2014). http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf (Page COL-A 4 of 5, COL-3, COL-4, COL-6, COL-7, COL-D). Accessed April 25, 2014.
  538. National Comprehensive Cancer Network (NCCN). Melanoma (Version 4.2014). http://www.nccn.org/professionals/physician_gls/pdf/melanoma.pdf. (Page ME-E 1 of 4). Accessed April 25, 2014.
  539. National Comprehensive Cancer Network (NCCN). Non-Small Cell Lung Cancer (NSCLC) (Version 3.2014). http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. (Page NSCL-A 3 of 4, NSCL-16, NSCL-H). Accessed April 25, 2014.
  540. National Comprehensive Cancer Network (NCCN). Non-Small Cell Lung Cancer (NSCLC) (Version 3.2014). http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. (Page NSCL-A 3 of 4). Accessed April 25, 2014.
  541. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. Version 2.2018, December 19, 2017. Accessed Sept 28, 2017: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
  542. National Comprehensive Cancer Network (NCCN). Practice Guidelines in colon cancer 2015 v2.0. Available at: http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf
  543. National Comprehensive Cancer Network (NCCN). Myelodysplastic Syndromes (MDS) (Version 2.2014). https://www.nccn.org/professionals/physician_gls/pdf/mds.pdf. (Page MDS-2). Accessed April 25, 2014.
  544. National Comprehensive Cancer Network (NCCN). Soft Tissue Sarcoma (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf (Page GIST-1, GIST-B, SARCB 3 of 3). Accessed April 25, 2014.
  545. National Comprehensive Cancer Network (NCCN). Thyroid Carcinoma (Version 4.2014). http://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. (Page MEDU-1, MEDU-2). Accessed April 25, 2014.
  546. Nault JC, Paradis V, Cherqui D, et al. Molecular classification of hepatocellular adenoma in clinical practice. J Hepatol. 2017; 67: 1074-1083.
  547. Navone NM, Troncoso P, Pisters LL, et al. p53 Protein accumulation and gene mutation in the progression of human prostate carcinoma. J Natl Cancer Inst. 1993; 85(20): 1657-1669. .
  548. Ng KL, Rajandram R, Morais C, et al. Differentiation of Oncocytoma From Chromophobe Renal Cell Carcinoma (RCC). J Clin Pathol. 2014;67(2): 97-104.
  549. Nguyen G-K, Lee MW, Ginsberg J, et al. Fine-needle aspiration of the thyroid: an overview. CytoJournal. 2005; 2:12.
  550. Niedzwiecki D FW, Venook AP, et al. Association between ColDx assay result and recurrence-free interval in Stage II colon cancer patients on CALGB (Alliance) 9581. ASCO-GI Annual Meeting January 16-18. 2014. Abst#455.
  551. Nielsen C, Birgens H, Nordestgaard B, Bojesen S. Diagnostic value of JAK2 V617F somatic mutation for myeloproliferative cancer in 49 488 individuals from the general population. British Journal of Haematology. 2012; 160: 70-79.
  552. Nielsen TO, Parker JS, Leung S, et al. A Comparison of PAM50 Intrinsic Subtyping with Immunohistochemistry and Clinical Prognostic Factors in Tamoxifen-Treated Estrogen Receptor-Positive Breast Cancer. Clin Cancer Res. 2010; 16: 5222.
  553. Nielsen T, Wallden B, Schaper C, et al. Analytical validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer. 2014; 14: 177.
  554. NIH/NCI draft guidelines presented on a poster at the Markers in Cancer meeting on October 11, 2012. Citation: J Clin Oncol. 2012 (suppl 30; abstr 58).
  555. Nikiforova MN, Mercurio S, Wald AI, et al. Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer. 2018;124: 1682-90.
  556. Nikiforova MN, Tseng GC, Steward D, et al. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. Journal of Clinical Endocrinology and Metabolism. 2008; 93, 1600–1608.
  557. Nikiforov YE, Carty SE, Chiosea SI, et al. Impact of the multi-gene ThyroSeq next-generation sequencing assay on cancer diagnosis in thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance cytology. Thyroid. 2015; 25(11): 1217-1223.
  558. Nikiforov YE, Ohori NP, Hodak SP, et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab. 2011; 96(11): 3390-7.
  559. Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules Journal of Clinical Endocrinology and Metabolism. 2009; 94: 2092–2098.
  560. Nodin B, Zendehrokh N, Sundstrom M, Jirstrom K. Clinicopathological correlates and prognostic significance of KRAS mutation status in a pooled prospective cohort of epithelial ovarian cancer. Diagnostic Pathology. 2013; 8: 106.
  561. Nogova L, Sequist LV, Perez Garcia JM, et al. Evaluation of BGJ398, a fibroblast growth factor receptor 1-3 kinase inhibitor, in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors: Results of a global phase I, dose-escalation and dose-expansion study. J Clin Oncol. 2017; 35(2): 157-165.
  562. Nout RA, Bosse T, Creutzberg CL, et al. Improved risk assessment of endometrial cancer by combined analysis of MSI, PI3K-AKT, Wnt/β-catenin and P53 pathway activation. Gynecologic Oncology. 2012; 126: 466-473.
  563. O'Connor ES, Greenblatt DY, LoConte NK, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011; 29(25): 3381-3388.
  564. Ohashi K, Sequist L, Arcila M, et al. Characteristics of lung cancers harboring NRAS mutations. Author Manuscript. Clin Cancer Res. 2013; 19(9): 2584–2591.
  565. Ohmoto A, Rokutan H, Yachida S. et al. Pancreatic neuroendocrine neoplasms: Basic biology, current treatment strategies and prospects for the future. Int J Mol Sci. 2017; 18(143): 1-16.
  566. Ohori NP, Nikiforova MN, Schoedel KE, et al. Contribution of Molecular Testing to Thyroid Fine-Needle Aspiration Cytology of ‘‘Follicular Lesion of Undetermined Significance/Atypia of Undetermined Significance.’’ Cancer Cytopathology. 2010; 118:17–23.
  567. Oien KA and Dennis JL. Diagnostic work-up of carcinoma of unknown primary: from immunohistochemistry to molecular profiling. Annals of Oncology. 2012; 23(10): 271-277. doi: 10.1093/annonc/mds357
  568. Olson R, Brastianos P, Palma D. Prognostic and Predictive Value of Epigenetic Silencing of MGMT in Patients with High Grade Gliomas: a Systematic Review and Meta-Analysis. J Neurooncol. 2011;105(2): 325-335.
  569. Oscier DG. Cytogenetic and Molecular Abnormalities in Chronic Lymphocytic Leukaemia. Blood Reviews. 1994; 8(2): 88-96.
  570. O’Sullivan P, Sharples K, Dalphin M, et. al. A Multigene Urine Test for the Detection and Stratification of Bladder Cancer in Patients Presenting with Hematuria. The Journal of Urology. 2012; 188: 741-747.
  571. Ousati Ashtiani Z, Mehrsai AR, Pourmand MR, et al. High resolution melting analysis for rapid detection of PIK3CA gene mutations in bladder cancer: A mutated target for cancer therapy. Urol J. 2018; 15(1): 26-31.
  572. Owen DH, Alexander AJ, Konda B, et al. Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of 06-methylguanine DNA methyltransferase as a biomarker for response. Oncotarget. 2017; 8(61): 104046-104056.
  573. Paik PK, Arcila ME, Fara M, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011; 29(15): 2046-51.
  574. Paik PK, Drilon A, Fan PD, et al. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutation causing Exon 14 skipping. Am Assoc Cancer Res. 2015; 8: 842-849.
  575. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. The New England Journal of Medicine. 2004; 351(27): 2817-2826.
  576. Paik S, Tang G, Shak S, et al. Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor–Positive Breast Cancer, J Clin Oncol. 2006; 24(23): 3726-3734.
  577. Pallante P, Battista S, Pierantoni GM, et al. Deregulation of microRNA expression in thyroid neoplasias. Nature Reviews of Endocrinology. 2014; 10: 88-101.
  578. Pallante P, Visone R, Ferracin M, et al. MicroRNA deregulation in human thyroid papillary carcinomas. Endocrine Related Cancer. 2006; 13: 497–508.
  579. Pálóczi K, Poros A, Szelenyi J, et al. TCR Gamma/Delta Bearing Lymphocytes in Peripheral Blood of Allogenic Bone Marrow Transplanted Patients. Leukemia. 1992; 6:(Suppl. 3).
  580. Palumbo A and Anderson K. Multiple Myeloma. NEJM. 2011; 364:1046-1060. Doi: 10.1056/NEJMra1011442
  581. Pandor A, Eggington S, Paisley S, et al. The clinical and cost effectiveness of oxaliplatin and capecitabine for the adjuvant treatment of colon cancer: systematic review and economic evaluation. Health Technol Assess. 2006; 10(41).
  582. Papaemmanuil E, Rapado I, Li Y, et al. RAG- Mediated Recombination is the Predominant Driver of Oncogenic Rearrangement in ETV6-RUNX1 Acute Lymphoblastic Leukemia. Nature Genetics. 2014; 46 (2): 116-125.
  583. Pardanani A, Reeder T, Kimlinger T, et al. Flt-3 and c-kit Mutation Studies in a Spectrum of Chronic Myeloid Disorders Including Systemic Mast Cell Disease. Leukemia Research. 2003; 27(8): 739-742.
  584. Park JY, Kim WY, Hwang TS, et al. BRAF and RAS Mutations in Follicular Variants of Papillary Thyroid Carcinoma. Endocrine Pathology. 2013; 24: 69-76.
  585. Park SJ, Lee TJ, Chang IH, et al. Role of the mTOR pathway in the progression and recurrence of bladder cancer: An immunohistochemical tissue microarray study. Korean J Urol. 2011; 52: 466-473.
  586. Parker JS, Mullins M, Cheang MC, et al. Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes. J Clin Oncol. 2009; 27: 1160-1167.
  587. Patel J, Gönen M, Figueroa M, et al. Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia. The New England Journal of Medicine. 2012; 366(12): 1079-1088.
  588. Patel SG, Carty SE, McCoy KL, et al. Preoperative detection of RAS mutation may guide extent of thyroidectomy. Surgery. 2017;161: 168-75.
  589. Patnaik MM, Hanson CA, Hodnefield JM, et al. Differential prognostic effect of IDH1 versus IDH2 mutations in myelodysplastic syndromes: a Mayo Clinic Study of 277 patients. Leukemia. 2012; 26: 101-105.
  590. Pfeifer H, Wassmann B, Pavlova A,  et al. Kinase Domain Mutations of BCR-ABL frequently Precede Imatinib-Based Therapy and Give Rise to Relapse in Patients with De Novo Philadelphia-positive Acute Lymphoblastic Leukemia (Ph ALL). Blood. 2007; 110 (2): 727-734.
  591. Pijnenborg JMA, van de Broek L, de Veen GCD, et al. TP53 overexpression in recurrent endometrial carcinoma. Gynecologic Oncology. 2006; 100: 397-404.
  592. Plamadeala V, Huang S, McCreary SM, et al. Analytical performance of a formalin-fixed paraffinembedded tissue-based 634-probe prognostic assay for predicting outcome of patients with stage II colon cancer. Appl Immunohistochem Mol Morphol. 2014; 22(4):308-316.
  593. Ponce C, de Lourdes F Chauffaille M, Ihara S, Silva M. MPL immunohistochemical expression as a novel marker for essential thrombocythemia and primary myelofibrosis differential diagnosis. Leukemia Research. 2012; 36: 93-97.
  594. Popoveniuc G, Jonklaas J. Thyroid nodules. Medical Clinics North America. 2012; 96:329-34.
  595. Postow MA, Carvajal RD. Therapeutic implications of KIT in melanoma. Cancer J. 2012; 18(2): 137-41.
  596. Prescott JD and Zeiger MA. The RET oncogene in papillary thyroid carcinoma. Cancer. 2015;121: 2137-2146.
  597. Poyet C, Hermanns T, Zhong Q, et al. Positive fibroblast growth factor receptor 3 immunoreactivity is associated with low-grade non-invasive urothelial bladder cancer. Oncology Letters. 2015; 10: 2753-2760.
  598. Pu X, Hildebrandt M, Lu C, et al. PI3K/PTEN/AKT/mTor pathway genetic variation predicts toxicity and distant progression in lung cancer patients receiving platinum-based chemotherapy. Author Manuscript. Lung Cancer. 2011 ; 71(1): 82–88.
  599. Puccetti E, Beissert T, Güller S, et al. Leukemia-associated Translocation Products Able to Activate RAS Modify PML and Render Cells Sensitive to Arsenic-Induced Apoptosis. Oncogene. 2003; 22: 6900-6907.
  600. Pulido M, Roubaud G, Cazeau AL, et al. Safety and efficacy of temsirolimus as second line treatment for patients with recurrent bladder cancer. BMC Cancer. 2018; 18(194): 1 -9.
  601. Qasem E, Murugan AK, Al-Hindi H, et al. TERT promoter mutations in thyroid cancer: a report from a middle eastern population. Endocrine-Related Cancer. 2015;22(6): 901-908.
  602. Pulido M, Roubaud G, Cazeau AL, et al. Safety and efficacy of temsirolimus as second line treatment for patients with recurrent bladder cancer. BMC Cancer. 2018; 18(194): 1 -9.
  603. QUASAR Collaborative Group: Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007; 370:2020-2029.
  604. Quinn DI, Henshall SM, Head DR, et al. Prognostic significance of p53 nuclear accumulation in localized prostate cancer treated with radical prostatectomy. Cancer Res. 2000; 60: 1585-1594.
  605. Rampurwala M, Rocque G, Burkard, M. Update on Adjuvant Chemotherapy for Early Breast Cancer. Breast Cancer: Basic and Clinical Research. 2014; 8: 125-133.
  606. Ratner ES, Keane FK, Lindner R, et al. A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer. Oncogene. 2012; 31: 4559-4566.
  607. Ravandi F, O’Brien S, Jones D, et al. T-Cell Prolymphocytic Leukemia: A Single-Institution Experience. Clinical Lymphoma & Myeloma. 2005; 6(3): 234-239.
  608. Ravdin P, Siminoff L, Davis G, et al. Computer Program to assist in making decisions about adjuvant therapy for women with early breast cancer. Journal of Clinical Oncology. 2001; 19(4): 980-991.
  609. Rebouisso S, Franconi A, Calderaro J, et al. Genotype-phenotype correlation of CTNNB1 mutations reveals different β-catenin activity associated with liver tumor progression. Hepatology. 2016; 64(6): 2047-2061.
  610. Rebouissou S, Herault A, Letoze E, et al. CDKN2A homozygous deletion is associated with muscle invasion in FGFR3-mutated urothelial bladder carcinoma. J Pathol. 2012; 227: 315-324.
  611. Reckamp KL. Targeted therapy for patients with metastatic non-small cell lung cancer. J Natl Compr Canc Netw. 2018; 16(5.5): 601-604.
  612. Ravdin P, Siminoff L, Davis G, et al. Computer Program to assist in making decisions about adjuvant therapy for women with early breast cancer. Journal of Clinical Oncology. 2001; 19(4): 980-991.
  613. Reeve T, Thompson NW. Complications of thyroid surgery: how to avoid them, how to manage them, and observations on their possible effect on the whole patient. World Journal of Surgery. 2000; 24: 971-5.
  614. Rekhtman N, Leighl NB, and Somerfield MR. Guideline Summary for Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors: American Society of Clinical Oncology endorsement of the College of American Pathologists/International Association for the study of lung cancer/association for molecular pathology guideline. J Clinical Oncology. 2014;32(32): 3673-3679.
  615. Rekhtman N, Pietanza MC, Hellmann MD, et al. Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma-like and non-small cell carcinoma-like subsets. Clin Cancer Res. 2016; 22(14): 3618-3629.
  616. Ricci C, Fermo E, Corti S, et al. RAS Mutations Contribute to Evolution of Chronic Myelomonocytic Leukemia to the Proliferative Variant. Clinical Cancer Research. 2010; 16(8): 2246-2256.
  617. Roche-Lestienne C, Lepers S, Soenen-Cornu V, et al.  Molecular Characterization of the Idiopathic Hypereosinophilic Syndrome (HES) in 35 French Patients with Normal conventional Cytogenetics. Leukemia. 2005; 19: 792-798.
  618. Rodriguez-Vida A, Saggese M, Hughes S, et al. Complexity of FGFR signaling in metastatic urothelial cancer. J Hematol Oncol. 2015; 8(119): 1-8.
  619. Roh MH, Yassin Y, Miron A, et al. High-grade fimbrial-ovarian carcinomas are unified by altered p53, PTEN and PAX2 expression. Modern Pathology. 2010; 23: 1316-1324.
  620. Romanus D, Cardarella S, Cutler D, et al. Cost-effectiveness of multiplexed predictive biomarker screening in non-small-cell lung cancer. J Thorac Oncol. 2015;10(4): 586-594.
  621. Rosatto L, Avenia N, Bernante P, et al. Complications of Thyroid Surgery: Analysis of a Multicentric Study on 14,934 Patients Operated on in Italy over 5 Years. World Journal of Surgery. 2004; 28(3):271-6.
  622. Rosenfeld N, Aharonov R, Meiri E, et al. MicroRNAs Accurately Identify Cancer Tissue Origin. Nature Biotechnology. 2008; 26: 462-469.
  623. Ross JS, Wang K, Al-Rohil RN, et al: Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy. Mod Pathol. 2014; 27: 271-280.
  624. Rossing M, Borup R, Henao R, et al. Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma. Journal of Molecular Endocrinology. 2012; 48, 11–23.
  625. Roupret M, Catto J, Coulet F, et al. Microsatellite instability as indicator of MSH2 gene mutation in patients with upper urinary tract transitional cell carcinoma. J Med Genet. 2004; 41: e91.
  626. Russo A, Sala P, Alberici P, et al. Prognostic Relevance of MLH1 and MSH2 Mutations in Hereditary Non-Polyposis Colorectal Cancer Patients. Tumori. 2009; 95(6): 731-738.
  627. Sabha N, Knobbe C, Maganti M, et al. Analysis of IDH Mutation, 1p/19q Deletion, and PTEN Loss Delineates Prognosis in Clinical Low-Grade Diffuse Gliomas. Neuro-Oncology. 2014; 16(7): 1-10.
  628. Sacher, R A. Gene expression profiling advances in multiple myeloma. HemOnc today. 2010; 11 (23).
  629. Sakai T, Nishida Y, Hamada S, et al. Immunohistochemical staining with non-phospho β-catenin as a diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with extra-peritoneal desmoid-type fibromatosis. Diagnostic Pathology. 2017; 12(66): 1-9.
  630. Salehian B and Samoa R. RET gene abnormalities and thyroid disease: who should be screened and when. J Clin Res Pediatr Endocrinol. 2013;5(S1): 70-78.
  631. Sanguedolce F, Cormio A, Bufo P, et al. Molecular markers in bladder cancer: Novel research frontiers. Crit Rev Clin Lab Sci. 2015; 52(5):242-255.
  632. Santarpia L, Myers JN, Sherman SI, et al. Genetic Alterations in the Ras/Raf/Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways in the Follicular Variant of Papillary Thyroid Carcinoma. Cancer. 2010; 116: 2974-83.
  633. Santoro M and Carlomagno F. Central role of RET in thyroid cancer. Cold Spring Harb Perspect Biol. 2013; 5: a009233. doi: 10.1101/cshperspect.a009233
  634. Santos I, Franzon C, Koga A. Laboratory Diagnosis of Chronic Myelomonocytic Leukemia and Progression to Acute Leukemia in Association with Chronic Lymphocytic Leukemia: Morphological Features and Immunophenotypic Profile. Rev Bras Hematol Hemoter. 2012; 34(3): 242-244.
  635. Sargent R, Jones D, Abruzzo L, et al. Customized Oligonucleotide Array-Based Comparative Genomic Hybridization as a Clinical Assay for Genomic Profiling of Chronic Lymphocytic Leukemia. Journal of Molecular Diagnostics. 2009; 77(1): 25-34.
  636. Schmitt AM, Pavel M, Rudolph T, et al. Prognostic and predictive roles of MGMT protein expression and promoter methylation in sporadic pancreatic neuroendocrine neoplasms. Neuroendocrinology. 2014; 100: 35-44.
  637. Schneider B, Riedel K, Zhivov A, et al. Frequent and yet unreported GNAQ and GNA11 mutations are found in uveal melanomas. Pathology and Oncology Research. 2017. https://doi.org/10.1007/s12253-017-0371-7
  638. Schnittger S, Bacher U, Haferlach C, et al. Characterization of NPM1-mutated AML with a history of myelodysplastic syndromes or myeloproliferative neoplasms. Leukemia. 2011; 25: 615-621.
  639. Schnittger S, Eder C, Jeromin S, et al. ASXL1 Exon 12 Mutations are Frequent in AML with Intermediate Risk Karyotype and are Independently Associated with an Adverse Outcome. Leukemia. 2013; 27(1): 82-91.
  640. Schrader J, Henes FO, Perez D, et al. Successful mTOR inhibitor therapy for a metastastic neuroendocrine tumour in a patient with a germline TSC2 mutation. Annals of Oncology. 2017; 28(4): 904-905.
  641. Schrag D, Rifas-Shiman S, Saltz L, et al. Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer. J Clin Oncol. 2002; 20(19):3999-4005.
  642. Schröder J, Kolkenbrock S, Tins J, et al. Analysis of Thrombopoietin Receptor (C-MPL) mRNA Expression in De Novo Acute Myeloid Leukemia. Leukemia Research. 2000; 24(5): 401-409.
  643. Schulz WA: Understanding urothelial carcinoma through cancer pathways. Int J Cancer. 2006; 119: 1513-1518.
  644. Schwarz JK, Payton JE, Rashmi R, et al. Pathway-Specific Analysis of Gene Expression Data Identifies the PI3K/Akt Pathway as a Novel Therapeutic Target in Cervical Cancer. Clin Cancer Res. 2012; 18: 1464-1471.
  645. Sempoux C, Bisig B, Couchy G, et al. Malignant transformation of a β-catenin inflammatory adenoma due to an S45 β-catenin-activating mutation present 12 years before. Human Pathology. 2017; 62: 122-125.
  646. Senkus E, Kyriakides S, Ohno S, et al. Primary Breast Cancer: ESMO Clinical Practice Guidelines. Annals of Oncology. 2015; 26(5): 8-30. doi:10.1093/annonc/mdv298
  647. Sepulveda A, Hamilton S, Allegra C, et al. Molecular biomarkers for the evaluation of colorectal cancer, guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. J Mol Diagn. 2017; 19(2); 187-225.
  648. Seront E, Rottey S, Sautois B, et al. Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers. Annals Oncology. 2012; 23(10): 2663.-70.
  649. Sestak I, Cuzick J. Markers for the identification of late breast cancer recurrence. Breast Cancer Research. 2015; 17(10): 1-8. DOI 10.1186/s13058-015-0516-0
  650. Sestak I, Cuzick J, Dowsett M, et al. Predication of Late Distant Recurrence After 5 years of Endocrine Treatment: A Combined Analysis of Patients From the Austrian Breast and Colorectal Cancer Study Group 8 and Arimidex, Tamoxifen Alone or in Combination Randomized Trials Using the PAM50 Risk of Recurrence Score. J Clin Oncol. 2014; 33: 916-922.
  651. Sestak I, Cuzick J, Dowsett M, et al. Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian Breast and Colorectal Cancer Study Group 8 and Arimidex, Tamoxifen Alone or in Combination randomized trials using the PAM50 risk of recurrence score. J Natl Cancer Inst. 2013; 105: 1504–11.
  652. Sestak I, Cuzick J, Dowsett M, et al. Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score. American Society of Clinical Oncology. 2015; 33(8): 916-925.
  653. Sestak I, Dowsett M, Zabaglo L, et al. Factors Predicting Late Recurrence for Estrogen Receptor-Positive Breast Cancer. J Natl Cancer Inst. 2013 (Advance Access published September 12, 2013).
  654. Sethakorn N and O’Donnell PH: Spectrum of genomic alterations in FGFR3: current appraisal of the potential role of FGFR3 in advanced urothelial carcinoma. BJU Int. 2016; 118: 681-691.
  655. Sfakianos JP, Cha Ek, Iyer G, Et al. Genomic characterization of upper tract urothelial carcinoma. Eur Urol. 2015; 68(6): 970-977.
  656. Sharma A, Yeow WS, Ertel A, et al. The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression. J Clin Invest. 2010; 120(12): 4478-4492.
  657. Shaughnessy Jr JD, Zhan F, Burington BE,  et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007; 109: 2276-2284. Epub 2006 Nov 14.
  658. Shaughnessy, JD et al. TP 53 deletion is not an adverse feature in multiple myeloma treated with total therapy 3. British Journal of Haematology. 2009; 147: 347-351.
  659. Sheu S-Y, Grabellus F, Schwertheim S, et al. Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours. British Journal of Cancer. 2010;102:376-382.
  660. Shih L-Y, Huang C-F, Lin T-L, et al. Heterogeneous Patterns of CEBPα Mutation Status in the Progression of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia to Acute Myelogenous Leukemia. Clin Cancer Res. 2005; 11: 1821-1826.
  661. Shoushtari AN and Carvajal RD. GNAQ and GNA11 mutations in uveal melanoma. Melanoma Research. 2014; 24: 525-534.
  662. Siemiatkowska A, Bieniaszewska M, Hellmann A, Limon J. JAK2 and MPL gene mutations in V617F-negative myeloproliferative neoplasms. Leukemia Research. 2010; 34: 387-389.
  663. Sikkema-Raddatz B, Johansson LF, de Boer EN, et al. Targeted Next-Generation Sequencing can Replace Sanger Sequencing in Clinical Diagnostics. Human Mutations. 2013; 34: 1035–1042.
  664. Simbolo M, Mafficini A, Sikora KO, et al. Lung neuroendocrine tumours: deep sequencing of the four World Health Organization histotypes reveals chromatin-remodelling genes as major players and a prognostic role for TERT, RB1, MEN1 and KMT2D. J Pathol. 2017; 241: 488-500.
  665. Simon R. Lost in Translation Problems and Pitfalls in Translating Laboratory Observations to Clinical Utility. Eur J Cancer. 2008; 44(18): 2707-2713.
  666. Simon R. Moving from correlative science to predictive oncology. EPMA Journal. 2010; 1: 377-387.
  667. Simon R, Paik S, Hayes D. Use of Archived specimens in evaluation or prognostic and predictive biomarkers. Commentaries JNCI. 2009; 101(21): 1446-1452.
  668. Simon R, Richter J, Wagner U, et al. High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer. Cancer Res. 2001; 61: 4514-4519.
  669. Skowronska A, Parker A, Ahmed G, et al. Biallelic ATM Inactivation Significantly Reduces Survival in Patients Treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 Trial. Journal of Clinical Oncology. 2012; 30 (36): 4524-4532.
  670. Smith DL, Lamy A, Beaudenon-Huibregtse S, et al. A Multiplex Technology Platform for the Rapid Analysis of Clinically Actionable Genetic Alterations and Validation for BRAF p.V600E Detection in 1549 Cytologic and Histologic Specimens. Archives of Pathology Laboratory Medicine. 2014; 138: 371–378.
  671. Sokol L, Caceres G, Rocha K, Stockero KJ, Dewald DW, List AF. JAK2V617F mutation in myelodysplastic syndrome (MDS) with del(5q) arises in genetically discordant clones. Leukemia Research. 2010; 34: 821-823.
  672. Sotlar K, Fridrich C, Mall A, et al. Detection of c-kit Point Mutation Asp-816 → Val in Microdissected Pooled Single Mast Cells and Leukemic Cells in a Patient with Systemic Mastocytosis and Concomitant Chronic Myelomonocytic Leukemia. Leukemia Research. 2002; 26(11): 979-984.
  673. Sorensen SV, Goh JW, Pan F, et al. Incidence-based cost-of-illness model for metastatic breast cancer in the United States. International Journal of Technology Assessment in Health Care. 2012; 28(1): 12-21.
  674. Spano J, Lagorce C, Atlan D, et al. Impact of EGFR expression on colorectal cancer patient prognosis and survival. Annals of Oncology. 2005; 16; 102-108.
  675. Spector Y, Fridman E, Rosenwald S, et al. Development and validation of a microRNA-based diagnostic assay for classification of renal cell carcinomas. Molecular Oncology. 2013; 7:732-738.
  676. Starczynowski DT, Vercauteren S, Telenius A, et.al. High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndrome reveals cryptic copy number alterations and predicts overall and leukemia-free survival. Blood. 2008; 112(8): 3412-3424. doi: 10.1182/blood-2007-11-122028
  677. Stinchcombe TE, Roder J, Peterman AH, et al. A Retrospective Analysis Of VeriStrat Status on Outcome of a Randomized Phase II Trial of First-Line Therapy with Gemcitabine, Erlotinib, or the Combination in Elderly Patients (Age 70 Years or Older) with Stage IIIB/IV Non-Small-Cell Lung Cancer. J Thorac Oncol. 2013; 8(4): 443-451.
  678. Stokowy T, Wojtas B, Krajewska J, et.al. A two miRNA classifier differentiates follicular thyroid carcinomas from follicular thyroid adenomas. Molecular Cell Endocrinology. 2015; 399: 43-49.
  679. Stoll SJ, Pitt SC, Liu J, et al. Thyroid Hormone Replacement after Thyroid Lobectomy. Surgery. 2009; 146(4): 554–560.
  680. Strimbu K, Tavel JA. What are Biomarkers? Current opinion in HIV and AIDS. 2010; 5(6): 463-466. doi:10.1097/COH.0b013e32833ed177
  681. Suh JH, Johnson A, Albacker L, et al. Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials. Oncologist. 2016; 21:684-691.
  682. Sun Ch, Chang YH, Pan CC, et al. Activation of the PI3K/Akt/mTor pathway correlates with tumour progression and reduced survival in patients with urothelial carcinoma of the urinary bladder. Histopathology. 2011; 58(7): 1054-1063.
  683. Surveillance, Epidemiology, and End Results (SEER). SEER Stat Fact Sheets: Colon and Rectum Cancer, 2015. Available at: http://seer.cancer.gov/statfacts/html/colorect.html
  684. Surveillance, Epidemiology, and End Results (SEER) Program. Cancer statistics review 1975-2011. Section 26. thyroid. http://seer.cancer.gov/csr/1975_2011 /browse_csr.php?sectionSEL=26&pageSEL=sect_26_table.22.html. Accessed on February 12, 2015
  685. Swierniak M, Wojcicka A, Czetwertynska M, et al. In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism. 2013; 98: E1401-1409.
  686. Takahashi K, Jabbour E, Wang X, et al. Dynamic acquisition of FLT3 or RAS alterations drive a subset of patients with lower risk MDS to secondary AML. Leukemia. 2013; 27: 2081-2083.
  687. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Annals of Internal Medicine. 1997; 126(3): 226-31.
  688. Tan HL, Sood A, Rhimi HA, et al. Rb Loss Is characteristic of prostatic small cell neuroendocrine carcinoma. Clin Cancer Res. 2014; 20(4): 890-903.
  689. Tanaka S, Miyagi S, Sashida G, et al. Ezh2 Augments Leukemogenicity by Reinforcing Differentiation Blockage in Acute Myeloid Leukemia. Blood.  2012; 120 (5): 1107-1117.
  690. Tasianakas A. Bohm MR, Getova V, et al. Skin metastases in metastatic uveal melanoma: GNAQ/GNA11 mutational analysis as a valuable tool. British Journal of Dermatology. 2013; 169: 160-163.
  691. Taye A, Guirciullo D, Miles BA, et al. Clinical performance of a next-generation sequencing assay (ThyroSeq v2) in the evaluation of indeterminate thyroid nodules. Surgery. 2018; 163(1): 97-103
  692. Technology Assessment on Genetic Testing or Molecular Pathology Testing of Cancers with Unknown Primary Site to Determine Origin (http://www.cms.gov/ medicare-coverage-database/details/ technology-assessments-details.aspx?& MEDCACId=67&bc= AAAIAAAAAAAAAA&TAId=90&)
  693. Tetzlaff MT, Liu A, Xu X, et al. Differential expression of miRNAs in papillary thyroid carcinoma compared to multinodular goiter using formalin fixed paraffin embedded tissues. Endocrine Pathology. 2007; 18: 163–173.
  694. The Cancer Genome Atlas Research Network. Integrated Genomic Characterization of Papillary Thyroid Carcinoma. Cell. 2014; 159: 676–690.
  695. Tournigand C, Andre T, Bonnetain F, et al: Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol. 2012; 30(27): 3353-3360.
  696. Thyroid Cancer. American Thyroid Association’s Clinical Thyroidology for the Public. 2017;10(8):12-13.
  697. Tricoli JV, Gumerlock PH, Yao JL, et al. Alterations of the retinoblastoma gene in human prostate adenocarcinoma. Genes Chromosomes Cancer. 1996; 15: 108-114.
  698. Tsianakas A, Bohm MR, Getova V, et al. Skin metastases in metastatic uveal melanoma: GNAQ/GNA11 mutational analysis as a valuable tool. British Journal of Dermatology. 2013; 169: 160-163.
  699. Tufano RP, Teixeira GV, Bishop J, Carson KA, Xing M. BRAF Mutation in Papillary Thyroid Cancer and Its Value in Tailoring Initial Treatment: A Systematic Review and Meta-Analysis. Medicine. 2012; 91(5): 274-286.
  700. Tunbridge,WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: The Whickham survey. Clinical Endocrinology (Oxford). 1977; 7: 481-493.
  701. Uegaki K, Kanamori Y, Kigawa J, et al. PTEN-positive and phosphorylated-Akt-negative expression is a predictor of survival for patients with advanced endometrial carcinoma. Oncology Reports. 2005; 14: 389-392.
  702. Ueland FR, Desimone CP, Seamon LG, et al. Effectiveness of a Multivariate Index Assay in the Preoperative Assessment of Ovarian Tumors. Obstet Gynecol. 2011; 117(6): 1289-97.
  703. Updated Clinical Utility Summary, dated 11/03/14 (Note: Original [or primary] study data is not presented in this summary, but just otherwise published results.)
  704. Vaiman M, Nagibin A, Hagag P, et al. Hypothyroidism following partial thyroidectomy. Otolaryngology: Head & Neck Surgery. 2008; 138(1): 98-100.
  705. Valderrabano P, Leon ME, Centeno BA, et al. Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests. European Journal of Endocrinology. 2016; 174(5): 621-629.
  706. van Amerongen RA, Retel VP, Coupe VMH, et al.  Next-generation sequencing in NSCLC and melanoma patients: a cost and budget impact analysis. Ecancermedicalscience. 2016; 10: 684: 1-16.
  707. van Broekhoven DL, Verhoef C, Grunhagen DJ, et al. Prognostic value of CTNNB1 gene mutation in primary sporadic aggressive fibromatosis. Ann Surg Oncol. 2015; 22: 1467-70.
  708. van den Bent M, Dubbink H, Yannick M, et al. IDH1 And IDH2 Mutations are Prognostic but not Predictive for Outcome in Anaplastic Oligodendroglial Tumors: A Report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res. 2010; 16(5): 1597-1604.
  709. van den Bent M, Gravendeel L, Gorlia T, et al. A Hypermethylated Phenotype is a Better Predictor of Survival than MGMT Methylation in Anaplastic Oligodendroglial Brain Tumors: A Report from EORTC Study 26951. Clin Cancer Res. 2011; 17(22): 7148-7155.
  710. Vander JB, Gaston EA, Dawber TR. The significance of nontoxic thyroid nodules. Final report of a 15-year study of the incidence of thyroid malignancy. Annals of Internal Medicine. 1968; 69: 537–540.
  711. van Oers JM, Zwarthoff EC, Rehman I, et al. FGFR3 mutations indicate better survival in invasive upper urinary tract and bladder tumours. Eur Urol. 2009; 55: 650-658.
  712. Van Raamsdonk CD, Bezrookove V, Green G, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009; 457: 599-602.
  713. Van Raamsdonk CD, Griewank KG, Crosby MB, et al. Mutations in GNA11 In uveal melanoma, N Engl J Med. 2010; 363(23):2191-2199.
  714. Van Rhijn BW, Lurkin I, Radvanyi F, et al. The fibroblast growth factor receptor 3 (FGFR3) mutation Is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res. 2001; 61: 1265-1268.
  715. van Rhijn BW, van der Kwast TH, Liu L, et al. The FGFR2 mutation is related to favorable pT1 bladder cancer. J Urol. 2012; 187: 310-314.
  716. Van Rhijn BW, Vis AN, van der Kwast TH, et al. Molecular Grading of Urothelial Cell Carcinoma With Fibroblast Growth Factor Receptor 3 and MIB-1 is Superior to Pathologic Grade for the Predication of Clinical Outcome. J Clin Oncol. 2003; 21(10): 1912-1921.
  717. Varadhachary GR, Abbruzzese JL, Lenzi R. Diagnostic Strategies for Unknown Primary Cancer. Cancer. 2004; 100: 1776-85.
  718. Varella-Garcia M, Brizard F, Roche J, et al. Aml1/ETO and Pml/RARA Rearrangements in a Case of AML-M2 Acute Myeloblastic Leukemia with t(15;17). Leukemia and Lymphoma. 1999; 33: 403-406.
  719. Verbruggen MB, Sieben NLG, Roemen GMJM, et al. v-Raf Murine Sarcoma Viral Oncogene Mutation Status in Serous Borderline Ovarian Tumors and the Effect on Clinical Behavior. Int J Gynecol Cancer. 2009; 19: 1560-1563.
  720. Verstovsek S. Advanced Systemic Mastocytosis: the Impact of KIT Mutations in Diagnosis, Treatment and Progression. European Journal of Haematology.  2013; 90(2): 89-98.
  721. Vijayvergia N, Boland PM, Handorf E, et al. Molecular profiling of neuroendocrine malignancies to identify prognostic and therapeutic markers: a Fox Chase Cancer Center pilot study. British Journal of Cancer. 2016; 115: 564-570.
  722. Villaruz LC, Socinski MA, Abberbock, S, et al. Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium. Cancer. 2015; 121:448-456.
  723. Viola D, Valerio L, Molinaro E, et al. Treatment of advanced thyroid cancer with targeted therapies: ten years of experience. Endocrine-Related Cancer. 2016;23: R185-R205.
  724. Viudez A, Carvalho FL, Maleki Z, et al. A new immunohistochemistry prognostic score (IPS) for recurrence and survival in resected pancreatic neuroendocrine tumors (PanNET). Oncotarget. 2016; 27(18): 24950-24961.
  725. Volante M, Rapa I, Gandhi M, et al. RAS Mutations Are the Predominant Molecular Alteration in Poorly Differentiated Thyroid Carcinomas and Bear Prognostic Impact. J Clin Endocrinol Metab. 2009; 94(12): 4735-4741.
  726. Wada H, Matsuda K, Akazawa Y, et al. Expression of somatostatin receptor type 2A and PTEN in neuroendocrine neoplasms is associated with tumor grade but not with site of origin. Endocr Pathol. 2016; 27: 179-187.
  727. Wallden B, Storhoff J, Nielsen T, et al. Development and verification of the PAM50-based Prosigna breast cancer gene signature assay. BMC Medical Genomics. 2015; 8: 54. doi:10.1186/s12920-015-0129-6.
  728. Walter M, Payton J, Ries R, et al. Acquired Copy Number Alterations in Adult Acute Myeloid Leukemia Genomes. PNAS. 2009; 106 (31): 12950-12955.
  729. Walter MJ, Ding L, Shen D, et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia. 2011; 25: 1153-1158.
  730. Walter RFH, Vollbrecht C, Christoph D, et al. Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors. Journal of Cancer. 2016; 7(15): 2165-2172.
  731. Walter T, van Brakel B, Vercherat C, et al. 06-Methylguanine-DNA methyltransferase status in neuroendocrine tumours: prognostic relevance and association with response to alkylating agents. British Journal of Cancer. 2015; 112: 523-531.
  732. Wang CC, Friedman L, Kennedy GC, et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid. 2011; 21:243–251.
  733. Wang H, Tso V, Wong C, et al. Development and validation of a highly sensitive urine-based test to identify patients with colonic adenomatous polyps. Clinical and Translational Gastroenterology. 2014; 5(e54): 1-8. doi:10:1038/ctg.2014.2.
  734. Wang L, Ignat A, and Axiotis CA. Differential expression of the PTEN tumor suppressor protein in fetal and adult neuroendocrine tissues and tumors: Progressive loss of PTEN expression in poorly differentiated neuroendocrine neoplasms. Applied Immunohistochemistry & Molecular Morphology. 2002; 10(2): 139-146.
  735. Wang Y and Dai B. PTEN genomic deletion defines favorable prognostic biomarkers in localized prostate cancer: a systematic review and meta-analysis. Int J Clin Exp Med. 2015; 8(4): 5430-5437.
  736. Wang X, Dai H, Wang Q, et al. EZH@ Mutations are Related to Low Blast Percentage in Bone Marrow and -7/del(7q) in De Novo Acute Myeloid Leukemia. PLOS ONE. 2013; 8 (4): 1-6.
  737. Ware Miller R, Smith A, DeSimone CP, et al. Performance of the American College of Obstetricians and Gynecologists' Ovarian Tumor Referral Guidelines With a Multivariate Index Assay. Obstet Gynecol. 2011; 117(6): 1298-306.
  738. Watanabe Y, Ueda H, Etoh T, et al. A Change in Promoter Methylation of hMLH1 is a Cause of Acquired Resistance to Platinum-based Chemotherapy in Epithelial Ovarian Cancer. Anticancer Research. 2007; 27: 1449-1452.
  739. Weisbrod AB, Zhang L, Jain M, et al. Altered PTEN, ATRX, CHGA, CHGB, and TP53 expression are associated with aggressive VHL- associated pancreatic neuroendocrine tumors. Horm Cancer. 2013; 4: 165-175.
  740. Wells Jr SA, Asa SL, Dralle H, et al. Revised American Thyroid Association Guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6): 567-610.
  741. Wolff EM, Liang G and Jones PA. Mechanisms of disease: genetic and epigenetic alterations that drive bladder cancer. Nature Clinical Practice Urology. 2005; 2(10): 502-510
  742. Xie H, Xie B, Lui C, et al. Association of PTEN expression with biochemical recurrence in prostate cancer: results based on previous reports. Onco Targets and Therapy. 2017; 10: 5089-5097.
  743. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nature Reviews: Cancer. 2013; 13: 184-99.
  744. Xiong W, Wu X, Starnes S, et al. An analysis of the clinical and biological significance of TP53 loss and the identification of potential novel transcriptional targets of TP 53 in multiple myeloma. Blood. 2008; 112(10): 4235-46.
  745. Yamada Y, Cancelas J. FIP1L1/PDGRa-Associated Systemic Mastocytosis. Int Arch Allergy Immunol. 2010; 152(suppl 1): 101-104.
  746. Yang J, Schnadig V, Logrono R, et al. Fine-needle aspiration of thyroid nodules: A study of 4703 patients with histologic and clinical correlations. Cancer (Cancer Cytopathology). 2007; 111(5): 306–15.
  747. Yang S, Wang X, Jiang H, et al. Effective treatment of aggressive fibromatosis with celecoxib guided by genetic testing. Cancer Biology & Therapy. 2017; 18(10): 757-760.
  748. Yang Y, Shao N, Luo G, et al. Mutations of PTEN Gene in Gliomas Correlate to Tumor Differentiation and Short-Term Survival Rate. Anticancer Research. 2010; 30(3): 981-986.
  749. Yassa L, Cibas ES, Benson CB, et al. Long-term Assessment of a Multidisciplinary Approach to Thyroid Nodule Diagnostic Evaluation. Cancer (Cancer Cytopathology). 2007; 111: 508–16.
  750. Yeganeh MZ, Sheikholeslami S, and Hedayati M. RET proto oncogene mutation detection and medullary thyroid carcinoma prevention. Asian Pac J Cancer Prev. 2015;16(6): 2107-2117.
  751. Yip L, Farris C, Kabaker AS, et al. Cost impact of molecular testing for indeterminate thyroid nodule fine-needle aspiration biopsies. Journal of Clinical Endocrinology and Metabolism. 2012; 97(6): 1905-12.
  752. Yip L. Molecular Markers for Thyroid Cancer Diagnosis, Prognosis, and Targeted Therapy. Journal of Surgical Oncology. 2015; 111: 43–50.
  753. Yip L, Wharry LI, Armstrong MJ, et al. A clinical algorithm for fine-needle aspiration molecular testing effectively guides the appropriate extent of initial thyroidectomy. Annals of Surgery. 2014; 260: 163–168.
  754. Yoon S-Y, Li C-Y, Tefferi A. Megakaryocyte c-Mpl expression in chronic myeloproliferative disorders and the myelodysplastic syndrome: immunoperoxidase staining patterns and clinical correlates. Eur J Haematol. 2000; 65: 170-174.
  755. Yuan ZM, Yang ZL, Zheng Q. Deregulation of microRNA expression in thyroid tumors. Journal of Zhejiang University Sciences B. 2014; 15: 212-224.
  756. Yun CH, Mengwasser KE, Toms AV, et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci. 2008; 105(6): 2070-2075.
  757. Zeng W, Nakao S, Takamatsu H, et al. Characterization of T-Cell Repertoire of the bone Marrow in Immune-Mediated Aplastic Anemia: Evidence for the Involvement of Antigen-Driven T-Cell Response in Cyclosporine-Dependent Aplastic Anemia. Blood. 1999; 93 (9): 3008-3016.
  758. Zenz T, Eichhorst B, Busch R, et al. TP53 Mutation and Survival in Chronic Lymphocytic Leukemia. Journal of Clinical Oncology. 2010; 28 (29): 4473-4479.
  759. Zhan F, Barlogie B, Mulligan G, et al. High-risk myeloma: a gene expression based risk-stratification model for newly diagnosed multiple myeloma treated with high-dose therapy is predictive of outcome in relapsed disease treated with single-agent bortezomib or high-dose dexamethazsone. Blood. 2008; 111: 968-969.
  760. Zhan F, Huang Y, Colla S,  et al. The molecular classification of multiple myeloma. Blood. 2006; 108: 2020-2028.
  761. Zhang GN, Liu H, Huang JM, et al. TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy in patients with advanced ovarian cancer. Gynecologic Oncology. 2014; 132(3): 752-757.
  762. Zhang HY, Zhang PN, Sun H. Aberration of the PI3K/AKT/mTOR signaling in epithelial ovarian cancer and its implication in cisplatin-based chemotherapy. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2009; 146: 81-86.
  763. Zhang Z and Wang M. PI3K/AKT/mTOR pathway in pulmonary carcinoid tumours. Oncology Letters. 2017; 14: 1373-1378.
  764. Zhou K, Jiang L, Shang Z,  et al. Potential Application of IDH1 and IDH2 Mutations as Prognostic Indicators in Non-Promyelocytic Acute Myeloid Leukemia: a Meta-Analysis. Leukemia & Lymphoma. 2012; 53: 2423-2429.
  765. Zhou Y, Barlogie B, Shaughnessy Jr JD. The molecular characterization and clinical management of multiple myeloma in the post genome era. Spotlight Review. Leukemia.  2009; 23: 1941-1956.
  766. Zhong Y, Chen B, Feng J,  et al. The Associations of Janus Kinase-2 (JAK2) A830G Polymorphism and the Treatment Outcomes in Patients with Acute Myeloid Leukemia. Leukemia & Lymphoma. 2010: 1115-1120.
  767. Zucman-Rossi J, Jeannot E, Nhieu JT, et al. Geontype-phenotype correlation in hepatocellular adenoma: New classification and relationship with HCC. Hepatology. 2006; 43: 515-524.
  768. http://www.accessdata.fda.gov/cdrh_docs/reviews/K081754.pdf
  769. http://www.accessdata.fda.gov/scripts/cdrh/ cfdocs/cftopic/pma/pma.cfm?num=p030052
  770. http://www.asco.org/ASCOv2/Practice+%26+ Guidelines/Guidelines/Clinical+Practice+Guidelines/ American+Society+of+Clinical+Oncology+ Provisional+Clinical+Opinion%3A+Epidermal+ Growth+Factor+Receptor+ %28EGFR%29+Mutation+Testing +for+Patients+with+Advanced+Non-Small+ Cell+Lung+Cancer+ Considering+First-Line+EGFR+Tyrosine-Kinase+ Inhibitor+%28TKI%29+Therapy
  771. http://www.cms.gov/medicare-coverage-database/ details/medcac-meeting-details.aspx? MEDCACId=67&bc=AAAIAAAAAAAAAA%3d%3d& (Minutes from this May 1, 2013 MEDCAC to be posted between July 1-September 1, 2013)
  772. http://www.egappreviews.org/recommendations/colorectal.htm
  773. http://www.fda.gov/MedicalDevices/Productsand MedicalProcedures/DeviceApprovalsand Clearances/Recently-ApprovedDevices/ ucm294907.htm
  774. http://www.fda.gov/NewsEvents/Newsroom /PressAnnouncements/ucm268241.htm
  775. http://www.fda.gov/NewsEvents/Newsroom /PressAnnouncements/ucm310899.htm
  776. http://www.gen-probe.com/products-services/progensa-pca3
  777. http://www.medscape.com/viewarticle/775368
  778. http://www.nationalcmlsociety.org/ living-cml/monitoring-tests
  779. http://www.nccn.org/professionals /biomarkers/default.asp
  780. http://www.novitas-solutions.com/webcenter/faces/ oracle/webcenter/page/scopedMD/ sad78b265_6797_4ed0_ a02f_81627913bc78/ Page41.jspx?wc.contextURL=%2Fspaces%2F MedicareJH&wc.originURL= %2Fspaces%2FMedicareJH%2Fpage%2F pagebyid&contentId =00024692&_afrLoop= 2523822121000#%40%3F_ afrLoop%3D2523822121000%26wc. originURL%3D%252Fspaces%252F MedicareJH%252Fpage% 252Fpagebyid%26 contentId%3D00024692%26wc. contextURL%3D%252 Fspaces%252F MedicareJH%26_adf.ctrl-state %3Dxegaeqb38_128

There were extensive in-person consultations with both CAC representatives and nationally-recognized experts in order to assist with the above medical necessity language and procedure-to-diagnosis code pairings.

Revision History Information

Revision History Date Revision History Number Revision History Explanation Reasons for Change
12/13/2020 R32

LCD revised and published on 11/5/2020 effective for dates of service on and after 12/13/2020 to update wording of utilization guidelines to appear as limitations.

  • Typographical Error
12/13/2020 R31

LCD posted for notice on 10/29/2020. LCD becomes effective for dates of service on and after 12/13/2020.

10/31/2019 DL35396 Draft LCD posted for comment.

  • Creation of Uniform LCDs With Other MAC Jurisdiction
07/01/2020 R30

LCD revised and published on 06/25/2020 effective for dates of service on and after 07/01/2020, as a non-discretionary update to remove limitations 1 and 3, these services will now be covered when medically reasonable and necessary and performed within the indications of the LCD consistent with CMS direction. Minor formatting changes have been made.

  • Other (revised in response to CMS direction)
11/14/2019 R29

LCD revised and published on 11/14/2019. Consistent with CMS Change Request 10901, the entire coding section has been removed from the LCD and placed into the related Billing and Coding Article, A52986. All CPT codes and coding information within the text of the LCD has been placed in the Billing and Coding Article.

  • Other (CMS Change Request 10901)
06/13/2019 R28

LCD revised and published on 06/27/2019. Per current LCD format, the 'Coding Information' statement has been placed after the Analysis of Evidence section. There has been no change in coverage with this LCD revision.

  • Typographical Error
06/13/2019 R27

LCD revised and published on 06/13/2019. Effective for dates of service on and after 03/27/2019 the following coding changes have been made in the related Billing and Coding Article (A52986); CPT code 81450 has been removed from CPT/HCPCS Code Group 2 and added to CPT/HCPCS Code Group 1 with no diagnosis to procedure code restrictions at this time. This coding change is a clarification, in response to an inquiry, since the LCD provides coverage for at least 5 of the biomarkers included in the service represented by 81450. Consistent with Change Request (CR) 10901 all CPT and ICD-10 codes have been removed from the LCD and placed in the related Billing and Coding Article, A52986. Language has been added in place of removed codes in Limitation #3. IOM citations for related NCDs have been added and the references have been moved to the Bibliography section. There has been no change in coverage with this LCD revision.

  • Other (Change in LCD process per CMS CR 10901; Inquiry)
04/04/2019 R26

LCD revised and published on 04/04/2019 effective for dates of service on and after 03/16/2018 to remove references to next generation sequencing due to implementation of NCD 90.2. Revised Molecular Test Indication related to Oncomine DX to refer to NCD 90.2. Removed CPT code 0022U from CPT/HCPCS Code Group 1, ICD-10 Group 2 Paragraph and Utilization Guidelines. NCD 90.2 listed as a Related National Coverage Document.

  • Other (New NCD)
01/01/2019 R25

LCD revised and published on 02/14/2019 effective for dates of service on and after 01/01/2019 to reflect the annual CPT/HCPCS code updates. The following CPT/HCPCS code(s) have been added to Group 1 Codes: 81233, 81236, 81237, 81305, 81320, and 81345. For the following CPT/HCPCS codes either the short description and/or the long description was changed. Depending on which description is used in this LCD, there may not be any change in how the code displays in the document: 81287, 81327, 81400, 81401, 81403, 81404, 81405, and 81407.

Covered Indications for Molecular Tests (#5) updated to include biomarker TERT for brain molecular biomarkers. ICD-10 Code Group #5 has been updated to include TERT reported with CPT code 81345. Utilization Guidelines have been updated to include the test for Brain Molecular Biomarkers (CPT code 81345) once per lifetime per beneficiary.

Covered Indications for Molecular Tests (#13) includes biomarker EZH2 for Myeloproliferative diseases. ICD-10 Code Groups #12, #16, and #22 have been updated to report EZH2 with CPT code 81236 or CPT code 81327.

Covered Indications for Molecular Tests (#13) updated to include biomarkers BTK and PLCG2 for Chronic lymphoid leukemia (CLL). ICD-10 Code Group #18 for CLL has been updated to include BTK reported with CPT code 81233 and PLCG2 reported with CPT code 81320.

Covered Indications for Molecular Tests (#13) updated to include biomarker MYD88 for Waldenstrom’s/Lymphoplasmacytic Lymphoma. New ICD-10 Code Group #28 for Waldenstrom’s/Lymphoplasmacytic Lymphoma has been added to include MYD88 reported with CPT code 81305. The following ICD-10 Code has been added for MYD88 reported with CPT code 81305 to ICD-10 Code Group 28: C88.0

CMS IOM language has been removed from the LCD per Change Request 10901.

  • Revisions Due To CPT/HCPCS Code Changes
  • Other (CMS Requirement)
10/04/2018 R24

LCD revised and published on 10/04/2018 to update the policy in response to inquiry and reconsideration requests; all literature reviewed and added to policy. Non-coverage reaffirmed for CPT codes 0012M and 0013M for CxBladder. Non-coverage reaffirmed for CPT code 0002U for PolypDx™ Assay and Algorithm. Effective for dates of service on and after 05/15/2018 the following changes have been made to the policy:

Covered Indications for Molecular Tests updated to include a new group (#4) for Uveal Melanoma with biomarkers GNAQ and GNA11. GNAQ is reported with CPT code 81403 and currently does not have ICD-10 diagnosis code pairing. The following ICD-10 diagnosis codes have been added for GNA11 reported with CPT code 81479 to ICD-10 Code Group 4: C69.01, C69.02, C69.11, C69.12, C69.21, C69.22, C69.31, C69.32, C69.41, C69.42, C69.51, C69.52, C69.61, C69.62, C69.81, C69.82.

ThyroSeq has been added to the thyroid test group (new group #6). CPT Code 0026U has been added to CPT Group 1 Codes. ThyroSeq for CPT code 0026U has been added to ICD-10 Code Group 6 (new) and added to the asterisk note indicating ICD-10 diagnosis codes C73 and D44.2 should not be reported for this test. Utilization Guidelines have been updated to include the ThyroSeq test once per lifetime per beneficiary.

Covered Indications for Molecular Tests updated to include biomarker FGFR3 as covered under Urinary Tract (new #9). FGFR3 is reported with CPT code 81404 and currently does not have ICD-10 code pairing.

Covered Indications for Molecular Tests updated to include biomarkers PTEN, RB1 and TP53 to Prostate (new group #10). TP53 is reported with CPT code 81405 and currently does not have ICD-10 code pairing. ICD-10 Code Group 9 (new) has been updated to include PTEN for CPT codes 81321, 81322, 81323 and RB1 for CPT code 81479.

Covered Indications for Molecular Tests updated to include biomarkers MGMT, PTEN, RB1, TP53 and TSC2 for Neuroendocrine tumors (new group #17). TP53 is reported with CPT code 81405 and currently does not have ICD-10 diagnosis code pairing. ICD-10 Code Group for neuroendocrine tumors (new #25) has been updated to include MGMT reported with CPT code 81287, PTEN reported with CPT codes 81321, 81322, or 81323; and RB1 or TSC2 reported with CPT code 81479.

Covered Indications for Molecular Tests updated to include biomarker CTNNB1 to Desmoid Fibromatosis (new group #19). CTNNB1 is reported with CPT code 81403 and currently does not have ICD-10 diagnosis code pairing.

Covered Indications for Molecular Tests updated to include biomarker CTNNB1 to Hepatic Adenoma (new group #20). CTNNB1 is reported with CPT code 81403 and currently does not have ICD-10 diagnosis code pairing.

Covered Indications for Molecular Tests updated to include biomarkers CDKN2A, FGFR3, PIK3CA and TP53 for Bladder (new group #21). CDKN2A, FGFR3, PIK3CA and TP53 reported with CPT code 81404 or 81405 and currently does not have ICD-10 diagnosis code pairing. CPT codes 81321, 81322 and 81323 for biomarker PTEN and CPT code 81479 for biomarkers FGFR1, MTOR and RB1 added to new ICD-10 Diagnosis Code Group 27 for Bladder. The following ICD-10 diagnosis codes have been added to new ICD-10 Code Group 27: C67.0, C67.1, C67.2, C67.3, C67.4, C67.5, C67.6, C67.7, C67.8 and C67.9.

Effective for dates of service on and after 05/18/2018, CPT code 0022U added to CPT Group 1 Codes. Utilization Guidelines and ICD-10 Code Group 2 updated to reflect Oncomine DX CPT code changed from 81445 to 0022U.

Covered Indications for Molecular Tests (#1) updated to include ColonSeq® for Colorectal Cancer and (#2) LungSeq® for Non-Small Cell Lung Cancer. ICD-10 Code Group 1 updated to add ColonSeq® for CPT code 81445. ICD-10 Code Group 2 updated to add LungSeq® for CPT code 81445.

In response to the annual ICD-10 code update, effective for dates of service 10/1/2018 and after the following ICD-10 codes have been deleted from ICD-10 code group 3: C43.11, C43.12, D03.11 and D03.12 and the following ICD-10 codes have been added to ICD-10 code group 3: C43.111, C43.112, C43.121, C43.122, D03.111, D03.112, D03.121, D03.122.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; therefore, not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To ICD-10-CM Code Changes
  • Reconsideration Request
07/26/2018 R23

LCD revised and published on 07/26/2018. The following revisions have been made in the covered indications section of the policy:

ThyGenX represented by CPT code 81445 has been added under Molecular Tests for Thyroid, ICD-10 Code Group Paragraph 5 and Utilization Guidelines effective for dates of service on and after 04/09/2018.

RosettaGX Reveal Thyroid miRNA has been added as a covered service under Molecular Tests for Thyroid, ICD-10 Code Group Paragraph 5 and Utilization Guidelines effective for dates of service on and after 04/09/2018. Literature submitted has been reviewed and added to the policy.

FLT3 D836 has been revised to FLT3 D835 under Molecular Tests for AML, CML/CMML and MDS covered indication sections. FLT3 D835 has also been removed from the following ICD-10 Code Group Paragraphs; Group 11, Group 16 and the newly numbered Group 21 (formerly group 22 before renumbering with this revision) since CPT 81246 does not have any diagnosis restrictions effective for dates of service 01/01/2015 and after.

Biomarker ATM listed under Molecular Tests for CLL covered indications has been removed from the LCD. This biomarker has also been removed from ICD-10 Code Group Paragraph 17 as there are no coverage restrictions for ATM at this time.

The CPT codes listed with IGH/BCL2 under Molecular Tests in the Follicular lymphoma section have been changed to 81401 and 81402. ICD-10 diagnosis code Group 18 has been deleted as 81401 and 81402 do not have any diagnosis limitations effective for dates of service on and after 01/01/2016. In response to removing Group 18 the ICD-10 code groups have been renumbered.

A clarifying statement has been added under the CPT Code Group 1 Paragraph to explain that these CPT codes do not have diagnosis limitations and providers should refer to the covered indications of the LCD for reasonable and necessary guidelines for biomarkers included in these CPT codes.

PIK3CA has been removed from the following ICD-10 Code Group Paragraphs list of biomarkers; Group 1, Group 4, Group 5 and Group 6 effective for dates of service on and after 01/01/2015.

Diagnosis codes C21.0, C21.2 and C21.8 have been added to ICD-10 Code Group 1 as covered diagnoses effective for dates of service on or after 12/01/2016.

Diagnosis code C55 has been added to ICD-10 Code Group 6 as a covered diagnosis effective for dates of service on or after 12/01/2016.

A typographical error was made during the ICD-9 to ICD-10 translation resulting in ICD-10 code C92.02 being placed in ICD-10 Code Group 10 instead of the correct ICD-10 code, C91.02. C92.02 is being deleted from ICD-10 Code Group 10 and C91.02 is being added effective for dates of service 12/01/2016 and after.

Diagnosis codes C93.10, C93.11 and C93.12 have been added to ICD-10 Code Group 16 as covered diagnoses effective for dates of service 12/01/2016 and after.

Diagnosis codes C91.60, C91.61 and C91.62 have been added to newly numbered ICD-10 Code Group 20 (formerly group 21 before renumbering with this revision) as covered diagnoses for T-cell leukemia effective for dates of service on or after 12/01/2016.

  • Typographical Error
  • Other (Recon, Inquiry)
03/08/2018 R22

LCD revised and published on 03/08/2018 effective for dates of service on and after 12/22/2017 to add limited coverage for Oncomine DX test reported with CPT code 81445 for Non-Small Cell Lung Cancer (NSCLC). Language has been added to #2 under Molecular Tests in the Covered Indications area and CPT code 81445 has been added to ICD-10 Group 2 Paragraph for NSCLC. Utilization guidelines have been added for the Oncomine DX test when reported with CPT code 81445. References received with a reconsideration request for the Oncomine DX test have been reviewed and added to the policy. Link to L36715-BRCA1 and BRCA2 Genetic Testing and L35062-Biomarkers Overview added to the Related Local Coverage Documents section. For provider education/guidance, per Annual Review, removed Bill Types 18x and 21x as those Bill Types are not for inpatient services claims; update to CFR listing per template.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; therefore, not all the fields included on the LCD are applicable as noted in this policy.

  • Reconsideration Request
  • Other (Annual Review)
01/01/2018 R21

LCD revised and published on 01/25/2018 effective for dates of service on and after 01/01/2018 to reflect the annual CPT/HCPCS code updates. For the following CPT/HCPCS codes either the short description and/or the long description was changed: 81400, 81401, 81403, 81404, 81405, 81406. Depending on which description is used in this LCD there may not be any change in how the code displays in the document. The following CPT/HCPCS codes have been added to CPT/HCPCS Code Group 1: 81120, 81121, 81175, 81176, 81334, 81520. The following CPT/HCPCS code has been deleted from CPT code group 1: 0008M. To clarify coverage for the new CPT/HCPCS code additions, ICD-10 Group Code Paragraphs have been updated as follows: Group 4: IDH1 (81120) and IDH2 (81121); Group 10: RUNX1 (81334); Group 11: ASXL1 (81175, 81176), IDH1 (81120), IDH2 (81121) and RUNX1 (81334); Group 15: ASXL1 (81175, 81176); Group 22: ASXL1 (81175, 81176), IDH1 (81120) and IDH2 (81121); and Group 24: 81520 has been added and 0008M has been deleted.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; therefore, not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To CPT/HCPCS Code Changes
11/09/2017 R20

LCD revised and published on 11/09/2017 effective for dates of service on and after 08/01/2017 to add the following new CPT/HCPCS codes for Proprietary Laboratory Analyses (PLA) to Group 2 CPT/HCPCS Codes as non-covered: 0009U, 0013U, 0014U, 0016U, and 0017U.  LCD revised with effective dates of service on and after 10/02/2017 to reflect the 4Q17 CPT/HCPCS code updates. For the following CPT/HCPCS code(s) either the short description and/or the long description was changed: 81405 and 0002U. Depending on which description is used in this LCD, there may not be any change in how the code displays in the document.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; therefore, not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To CPT/HCPCS Code Changes
10/01/2017 R19

LCD revised and published on 10/05/2017 effective for dates of service on and after 10/01/2017 to reflect the ICD-10 Annual Code Updates.  The following ICD-10 code has been deleted from Group 20 codes: C96.2. The following ICD-10 codes have been added to Group 20 codes: C96.20, C96.22, C96.29.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; therefore, not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To ICD-10-CM Code Changes
08/10/2017 R18

LCD revised and published on 08/10/2017 effective for dates of service on and after 05/01/2017 to add the following CPT code as non-covered to Group 2 Codes: 0005U.

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

  • Revisions Due To CPT/HCPCS Code Changes
02/01/2017 R17

LCD revised and published on 07/13/2017 to add references received with a reconsideration request for CxBladder coverage. After review of the submitted literature it has been determined that non-coverage of CxBladder will remain.  No substantial changes are being made to the LCD at this time. 

At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage which requires comment and notice. This revision is not a restriction to the coverage determination; and, therefore not all the fields included on the LCD are applicable as noted in this policy.

 

  • Reconsideration Request
02/01/2017 R16 LCD revised and published on 05/11/2017 effective for dates of service on and after 02/01/2017 to add the following CPT codes as non-covered to Group 2 Codes: 0002U and 0003U. An explanation of non-coverage for these codes has been added to the Limitation section of the policy.
  • Revisions Due To CPT/HCPCS Code Changes
01/01/2017 R15 LCD revised and published on 01/12/2017 effective for dates of service on and after 01/01/2017 to reflect the annual CPT/HCPCS code updates. For the following CPT/HCPCS codes either the short description and/or the long description was changed. Depending on which description is used in this LCD, there may not be any change in how the code displays in the document: 81402 and 81407. The following CPT/HCPCS code 81327 has been added to group 1 CPT codes and Group 1 Paragraph for ICD-10 codes of the LCD.
  • Revisions Due To CPT/HCPCS Code Changes
12/01/2016 R14 LCD posted for notice on 10/13/2016. LCD becomes effective for dates of service and after 12/01/2016.

05/19/2016 DL35396 Draft LCD posted for comment.
  • Automated Edits to Enforce Reasonable & Necessary Requirements
10/01/2016 R13 LCD revised and published on 09/29/2016 effective for dates of service on and after 10/01/2016 to reflect the ICD-10 Annual Code Updates. The following ICD-10 codes have been added to the list of Group 8 diagnosis codes: N42.31, N42.32 and N42.39. The following ICD-10 codes have been added to Group 9 diagnosis codes: C49.A0, C49.A1, C49.A2, C49.A3, C49.A4, C49.A5 and C49.A9. The following Group 8 ICD-10 codes have undergone a descriptor change: N40.0 and N40.1.
  • Revisions Due To ICD-10-CM Code Changes
01/22/2016 R12 LCD revised and published on 05/12/2016 to correct source for Starczynowski.
  • Typographical Error
01/22/2016 R11 LCD revised and published on 04/14/2016, effective for dates of service 01/22/2016, to add limited coverage for Prosigna upon additional reconsideration request. A new Group for CPT/HCPCS code 0008M was created for the following ICD-10 codes for 0008M: C50.011, C50.012, C50.019, C50.111, C50.112, C50.119, C50.211, C50.212, C50.219, C50.311, C50.312, C50.319, C50.411, C50.412, C50.419, C50.511, C50.512, C50.519, C50.611, C50.612, C50.619, C50.811, C50.812, C50.819, C50.911, C50.912, C50.919. Submitted sources have been added to the LCD. Please note: The content of this LCD version remains the same as the prior version (R10) except that additional codes have been added to the Revision History for this version to accurately reflect all the code additions.
  • Reconsideration Request
01/22/2016 R10 LCD revised and published on 04/14/2016, effective for dates of service on and after 01/22/2016, to add limited coverage for Prosigna upon additional reconsideration request. A new Group for CPT/HCPCS code 0008M was created for the following ICD-10 codes for 0008M: C50.011, C50.012, C50.111, C50.112, C50.211, C50.212, C50.311, C50.312, C50.411, C50.412, C50.511, C50.512, C50.611, C50.612, C50.811, C50.812, C50.911, C50.912. Submitted sources have been added to the LCD.
  • Reconsideration Request
01/01/2016 R9 LCD revised and published on 02/11/2016, effective for dates of service 12/14/2015 and after, to add coverage for ThyraMIR services reported with CPT code 81479. The following ICD-10 codes have been added to Group 5 for ThyraMIR: E01.0, E01.2, E04.0, E04.8, E04.9.
  • Reconsideration Request
01/01/2016 R8 LCD revised and published on 01/28/2016 to reflect the annual CPT/HCPCS code updates. For the following CPT/HCPCS codes, either the short description or the long description was changed. Depending on which description is used in this LCD, there may not be any change in how the code displays in the document: 81210, 81275, 81402, 81435, 81436, 81445, 81450. The following code has been added to CPT group 2 as NON-COVERED; 81595 as the service represented by this code is currently non-covered per the LCD under the non-conventional methods of NGS limitation. CPT code 81170 has been added to groups 10 and 16 to replace 81403 for reporting ABL1. CPT code 81218 has been added to groups 11 and 23 to replace 81403 for CEBPA. CPT code 81272 has been added to groups 3 and 9 to replace 81404 for KIT. CPT 81273 has been added to groups 11, 16, 19, 21, and 23 to replace 81402 for KIT. CPT 81276 has been added to groups 1, 2, 5, 6, 11, 16, and 23. CPT code 81311 has been added to groups 1, 3, 5, 11, 16, and 23 to replace 81404 associated with NRAS. CPT code 81314 has been added to group 9 to replace 81404 associated with PDGFRA. CPT code 81538 has been added for VeriStrat® testing to group 2 diagnosis.
  • Revisions Due To CPT/HCPCS Code Changes
10/01/2015 R7 LCD revised and published on 11/13/2015 to add ICD-10 diagnosis codes with higher specificity to Group 5 effective for dates of service on and after 10/01/2015. Diagnosis codes added to Group 5: D44.2, D44.9, E01.1. Sources from reconsideration requests have been reviewed and added to the LCD sources. No substantial changes have been made based on the reconsiderations.
  • Reconsideration Request
  • Other (Clarification)
10/01/2015 R6 LCD revised and published on 10/08/2015 to reflect that OVA1 should be reported with CPT 81503 rather than 84999 effective for dates of service on and after 10/01/2015.
  • Revisions Due To CPT/HCPCS Code Changes
10/01/2015 R5 LCD revised and published on 08/13/2015 to add multiple sources submitted with several reconsideration requests regarding Prosigna, molecular kidney cancer testing and bladder cancer testing. All literature was reviewed. No changes to the policy were made based on these reconsideration requests.
  • Reconsideration Request
10/01/2015 R4 LCD revised and published on 01/23/2015 to reflect the annual CPT/HCPCS code updates For the following CPT/HCPCS code(s) either the short description and/or the long description was changed. Depending on which description is used in this LCD, there may not be any change in how the code displays in the document: 81245; 81402; 81403; 81404; 81405. The following codes have been added to CPT group 2 as NON-COVERED; 81445, 81450 and 81455.The following codes have been added to the LCD but will not have any diagnosis to procedure code editing at this time; 81246; 81435; and 81436.CPT code 81313 has been added to group 8 to replace 81479 for reporting PROGENSA® PCA3 Assay. Original and subsequent decisions to non-cover Prosigna are reaffirmed upon additional reconsideration request. Submitted sources have been added to the LCD.
  • Revisions Due To CPT/HCPCS Code Changes
  • Reconsideration Request
10/01/2015 R3 LCD revised and published on 10/09/2014, effective for dates of service on or after 10/01/2015. Non-coverage for Prosigna reaffirmed upon reconsideration request. LCD revised to add ICD-10-CM codes under group 5 for indeterminate malignancy, as well as presumed or documented malignancy of the thyroid gland per a reconsideration request. LCD also revised to add limited coverage for MyPRS multiple myeloma testing.
  • Reconsideration Request
10/01/2015 R2 10/01/2014 LCD revised and published on 08/14/2014 to provide clarifications to the statement regarding next generation sequencing methods in the limitations section and to the cancer of unknown primary testing area. Reference to Local Coverage Article A52986 was inserted into LCD.
  • Typographical Error
10/01/2015 R1 10/01/2014 LCD revised and published on 08/14/2014 to provide clarifications to the statement regarding next generation sequencing methods in the limitations section and to the cancer of unknown primary testing area. Reference to Local Coverag Article A52986 was inserted into LCD.
  • Other (Clarification)
N/A

Associated Documents

Attachments
N/A
Related National Coverage Documents
N/A
Public Versions
Updated On Effective Dates Status
10/30/2020 12/13/2020 - N/A Currently in Effect You are here
10/23/2020 12/13/2020 - N/A Superseded View
Some older versions have been archived. Please visit the MCD Archive Site to retrieve them.

Keywords

N/A

Read the LCD Disclaimer