Predictive Biomarkers in Thyroid Cancer

Abstract

In molecular pathology, predictive biomarkers identify which patients are likely to respond to targeted drugs. These therapeutic agents block specific molecules directly involved in cancer growth, dedifferentiation and progression. Until few years ago, the only targeted drugs available for advanced thyroid cancer included multi-tyrosine kinase inhibitors, mainly targeting the MAPK pathway and the angiogenic signaling. The administration of these drugs does not necessarily require a molecular characterization of tumors to assess the presence of predictive alterations. However, the availability of new selective targeted drugs for thyroid cancer patients is changing the diagnostic strategies for the molecular characterization of these tumors. The search for targetable alterations can be performed directly on tumor tissue by using a variety of methodologies, depending also on the number and type of alterations to test (i.e. single nucleotide variation or gene rearrangement). Herein, a comprehensive review of the currently available targeted treatments for thyroid cancer, related predictive markers and testing methodologies is provided.

Keywords: molecular marker; molecular pathology; predictive marker; targeted therapy; thyroid cancer.

Figure 1

Representative histological slides of thyroid cancer subtypes (hematoxylin/eosin stain). (A) papillary thyroid carcinoma (original magnification 20X); (B) poorly differentiated thyroid carcinoma with insular growth pattern (original magnification 4X); (C) anaplastic thyroid carcinoma (original magnification 20X); (D) medullary thyroid carcinoma (original magnification 10X).

Figure 2

Algorithm for molecular diagnostics of predictive markers in thyroid cancer. ATC, anaplastic thyroid cancer; DTC, differentiated thyroid cancer; sMTC, sporadic medullary thyroid cancer; MSI, microsatellite instability; NGS, next-generation sequencing.