Advances and practical use of the molecular markers for thyroid cancer

Abstract

Background : Thyroid nodules are very common; however, only 5–15% of nodules are malignant. Although most of the malignant thyroid cancers can be identified pre-operatively by cytological analysis, approximately 20–30% of these nodules are classified indeterminate. Subsequently, repeated Fine Needle Aspiration (FNA) or thyroid surgery may be required for a more definitive diagnosis. In the United States, the incidence of thyroid cancer has tripled from 1975 with an incidence rate of 14.3 per 100,000 individuals, primarily due to an increased diagnosis of papillary thyroid cancer which increased by 9.1 per 100,000 (RR 3.7, 95% CI (3.4–4.0)); however, mortality has remained stable. Many patients with cytologically indeterminate nodules undergo unnecessary diagnostic surgeries, placing them at risk of potential surgical complications and need for lifelong levothyroxine replacement. The advent of molecular gene testing has drawn significant attention toward improved stratification of these indeterminate lesions into benign or malignant. Detection of any pertinant molecular mutations in the indeterminate categories- atypia of undetermined significance (AUS)/ follicular lesion of undetermined significance (FLUS), follicular neoplasm (FN)/suspicious for a follicular neoplasm (SFN), and suspicious for malignant cells (SMC) has been shown to confer the risk of histologic malignancy of 88, 87 and 95% respectively, while a negative test for the mutation was reassuring with a very high negative predictive value over 95%. Purpose : The purpose of this article is to review the current recommendations to implement molecular genetic testing for thyroid nodules. We review the most common gene mutations harbored in the various thyroid cancers, including BRAF, RAS, and RET/PTC. We will also review the more recently discovered gene mutations for thyroid cancer, including TERT mutations. Finally, we will discuss the practice guidelines to implement molecular gene testing for the indeterminate cytology of thyroid nodules as well as the new category of non-invasive follicular thyroid neoplasm with papillary-like nuclear features as an intermediate pathology which will not require aggressive therapy after diagnostic lobectomy. (Published: 13 December 2016) Citation: Advances in Cellular and Molecular Otolaryngology 2016, 4: 33948 - http://dx.doi.org/10.3402/acmo.v4.33948