Molecular testing for thyroid nodules: Review and current state

Abstract

Thyroid nodules affect nearly two-thirds of the world population. Fine-needle biopsy with cytologic evaluation remains the diagnostic test of choice to distinguish benign from malignant thyroid nodules yet fails to discriminate as benign or malignant in up to one-third of cases. This review discusses the limitation of current cytopathologic evaluation, the development of thyroid molecular testing, and the strengths and limitations of commercially available tests. Initial cytomolecular testing sought to identify specific gene mutations associated with thyroid cancer. Although the presence of a mutation was strongly associated with cancer, the likelihood of identifying a mutation was low; therefore, the test had low sensitivity. Subsequent tests developed have sought to improve the accuracy of cytomolecular testing for thyroid fine-needle aspirations, both to reassure patients and providers when malignancy may be absent and to confirm the malignancy when present. The development of cytomolecular testing for thyroid nodules has informed and improved current understanding of thyroid nodule formation and progression. When used appropriately and with clear understanding of the advantages and disadvantages, cytomolecular testing has the potential to improve patient care in the setting of indeterminate thyroid nodules by helping to guide both the need for and the extent of thyroid surgery. Cancer 2018;124:888-98. © 2017 American Cancer Society.

Risk of malignancy and neoplasia predicted by three molecular testing platforms in indeterminate thyroid nodules on fine‐needle aspiration

“…There has been a noticeable shift toward more conservative management and personalized medicine . Ancillary molecular testing is often endorsed as a supplement to enhance the diagnostic yield of FNAs with indeterminate cytology . The 2015 American Thyroid Association (ATA) guidelines clearly address the utility of molecular markers and recommend their use with indeterminate aspirates …”

“…We previously conducted a retrospective study to evaluate the use of direct smears with these platforms . Both algorithms incorporate testing for microRNAs (miRNAs), which are involved in regulating gene transcription and cellular function . Several publications have reported unique patterns of miRNA expression in different tumors, including thyroid cancer …”

“…It utilizes the same four DNA point mutations and three RNA translocation fusion markers that are reported to be highly specific for differentiated thyroid cancer. With its release in 2014, ThyGenX applied next‐generation sequencing to include more than 100 genetic alterations across 8 genes (Table ) …”

“…ThyraMIR is a molecular assay released in 2015 and designed as a reflex test after ThyGenX. Its purpose is to analyze samples that are negative for the oncogene panel and those that are positive for changes other than BRAF V600E and RET/PTC‐1/3 . ThyraMIR evaluates the expression of 10 different miRNAs to further modify the risk of malignancy.…”

“…ThyraMIR evaluates the expression of 10 different miRNAs to further modify the risk of malignancy. It utilizes a proprietary algorithm to classify indeterminate aspirates along a spectrum ranging from a low‐risk to high‐risk profile (Table ) …”