Get access

Diagnosis and management of differentiated thyroid cancer using molecular biology

Authors

  • Robert L. Witt MD,

    Corresponding author
    1. Department of Surgery, Helen F. Graham Cancer Center, Christiana Care, Newark, Delaware and the Department of Otolaryngology-Head & Neck Surgery, Thomas Jefferson University (R.L.W.), Philadelphia, Pennsylvania
    • 4745 Ogletown-Stanton Rd., MAP #1, # 112, Newark DE 19713

    Search for more papers by this author
  • Robert L. Ferris MD,

    1. Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh (R.L.F.), Pittsburgh, Pennsylvania; Department of Otolaryngology-Head & Neck Surgery, Thomas Jefferson University (E.A.P.), Philadelphia, Pennsylvania
    Search for more papers by this author
  • Edmund A. Pribitkin MD,

    1. Department of Endocrine Neoplasia and Hormonal Disorders, the MD Anderson Cancer Center (S.I.S.), Houston, Texas
    Search for more papers by this author
  • Steven I. Sherman MD,

    1. Department of Otolaryngology-Head & Neck Surgery and Department of Medicine, Division of Endocrinology, University of Cincinnati (D.L.S.), Cincinnati, Ohio
    Search for more papers by this author
  • David L. Steward MD,

    1. Department of Pathology and Laboratory Medicine, University of Pittsburgh (Y.E.N.), Pittsburgh, Pennsylvania, U.S.A.
    Search for more papers by this author
  • Yuri E. Nikiforov MD, PhD

    1. Department of Otolaryngology-Head & Neck Surgery, University of Pittsburgh (R.L.F.), Pittsburgh, Pennsylvania; Department of Otolaryngology-Head & Neck Surgery, Thomas Jefferson University (E.A.P.), Philadelphia, Pennsylvania
    Search for more papers by this author

  • Edmund A. Pribitkin, MD, is a consultant for Stryker Corporation. Steven I. Sherman, MD, and David L. Steward, MD, are consultants for Veracyte. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis:

To define molecular biology in clinical practice for diagnosis, surgical management, and prognostication of differentiated thyroid cancer.

Data Sources:

Ovid Medline 2006-2012

Review Methods:

Manuscripts with clinical correlates.

Results:

Papillary thyroid carcinomas harbor point mutations of the BRAF and RAS genes or RET/PTC rearrangements, all of which activate the mitogen-activated protein kinase pathway. These mutually exclusive mutations are found in 70% of PTC. BRAF mutation is found in 45% of papillary thyroid cancer and is highly specific. Follicular carcinomas are known to harbor RAS mutation or PAX8/PPARγ rearrangement. These mutations are also mutually exclusive and identified in 70% of follicular carcinomas. Molecular classifiers measure the expression of a large number of genes on a microarray chip providing a substantial negative predictive value pending further validation.

Conclusions:

1) 20% to 30% of cytologically classified Follicular Neoplasms and Follicular Lesion of Undetermined Significance collectively are malignant on final pathology. Approximately 70% to 80% of thyroid lobectomies performed solely for diagnostic purposes are benign. Molecular alteration testing may reduce the number of unnecessary thyroid procedures, 2) may reduce the number of completion thyroidectomies, and 3) may lead to more individualized operative and postoperative management. Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ for follicular lesion of undetermined significance and follicular neoplasm improve specificity, whereas molecular classifiers may add negative predictive value to fine needle aspiration diagnosis.

Ancillary