The role of molecular genetics in the pre-surgical management of thyroid nodules

Abstract

Introduction Fine-needle aspiration (FNA) is an important diagnostic tool for the evaluation of thyroid nodules. However in almost ¼ of all nodules submitted to FNA cytology is indeterminate. Since the majority of genetic alterations in thyroid cancer have been identified, the use of molecular testing platforms has been endorsed by American Thyroid Association (ATA) for management of indeterminate nodules. Evidence acquisition Several commercial tests are based on mRNA expression of FNA samples (Afirma ®) while others detect DNA alterations (ThyroSeq). Non commercial tests detect limited number of point mutations or re-arrangements (gene panels). Evidence synthesis Gene expression profile tests serve as "rule out" tests due to their high NPV and perform better in a setting of low cancer pre-test probability. Genetic alteration platforms display high PPV and serve as rather "rule in" tests but their diagnostic accuracy is hampered either because a small proportion of nodules does not harbor any of these alterations targeted (gene panels) or because commonly identified RAS mutations can also be found in benign nodules. Conclusions Next Generation Sequencing NGS) development and incorporation of other genetic markers such as miRNA can improve diagnostic accuracy of molecular tests.