Molecular Diagnostics of Thyroid Tumors

Abstract

Abstract Context.—Thyroid cancer is the most common type of endocrine malignancy and its incidence is steadily increasing. Papillary carcinoma and follicular carcinoma are the most common types of thyroid cancer and represent those tumor types for which use of molecular markers for diagnosis and prognostication is of high clinical significance. Objective.—To review the most common molecular alterations in thyroid cancer and their diagnostic and prognostic utility. Data Sources.—PubMed (US National Library of Medicine)–available review articles, peer-reviewed original articles, and experience of the author. Conclusions.—The most common molecular alterations in thyroid cancer include BRAF and RAS point mutations and RET/PTC and PAX8/PPARγ rearrangements. These nonoverlapping genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. These molecular alterations can be detected in surgically resected samples and fine-needle aspiration samples from thyroid nodules and can be of significant diagnostic use. The diagnostic role of BRAF mutations has been studied most extensively, and recent studies also demonstrated a significant diagnostic utility of RAS, RET/PTC, and PAX8/PPARγ mutations, particularly in thyroid fine-needle aspiration samples with indeterminate cytology. In addition to the diagnostic use, BRAF V600E mutation can also be used for tumor prognostication, as this mutation is associated with higher rate of tumor recurrence and tumor-related mortality. The use of these and other emerging molecular markers is expected to improve significantly the accuracy of cancer diagnosis in thyroid nodules and allow more individualized surgical and postsurgical management of patients with thyroid cancer.