Emerging Biomarkers in Thyroid Practice and Research

Abstract

Thyroid cancer is the most common endocrine malignancy. Recent developments in molecular biological techniques have led to a better understanding of the pathogenesis and clinical behavior of thyroid neoplasms. This has culminated in the updating of thyroid tumor classification, including the re-categorization of existing and introduction of new entities. In this review, we discuss various molecular biomarkers possessing diagnostic, prognostic, predictive and therapeutic roles in thyroid cancer. A comprehensive account of epigenetic dysregulation, including DNA methylation, the function of various microRNAs and long non-coding RNAs, germline mutations determining familial occurrence of medullary and non-medullary thyroid carcinoma, and single nucleotide polymorphisms predisposed to thyroid tumorigenesis has been provided. In addition to novel immunohistochemical markers, including those for neuroendocrine differentiation, and next-generation immunohistochemistry (BRAF V600E, RAS, TRK, and ALK), the relevance of well-established markers, such as Ki-67, in current clinical practice has also been discussed. A tumor microenvironment (PD-L1, CD markers) and its influence in predicting responses to immunotherapy in thyroid cancer and the expanding arena of techniques, including liquid biopsy based on circulating nucleic acids and plasma-derived exosomes as a non-invasive technique for patient management, are also summarized.

Update on International Medical Taxonomies of Biomarkers and Their Applications in Management of Thyroid Cancers

“…Currently, Sorafenib-tosylate, Doxorubicin-hydrochloride, Vandetanib, Cabozantinib-s-malate, Dabrafenib-mesylate, Trametinib-dimethyl-sulfoxide, Lenvatinibmesylate, Pralsetinib and Selpercatinib have been validated to be used as drugs targeting molecules. This is because of their ability to recognize specific molecules expressed on the cancerous tissues of patients [33][34][35]. By targeting serine/threonine and tyrosine kinases such as RAF1, BRAF, VEGFR 1, 2, 3, PDGFR, KIT, FLT3, FGFR1 and RET, these compounds inhibit tumor cell proliferation and angiogenesis (Table 2) [33][34][35].…”

“…This is because of their ability to recognize specific molecules expressed on the cancerous tissues of patients [33][34][35]. By targeting serine/threonine and tyrosine kinases such as RAF1, BRAF, VEGFR 1, 2, 3, PDGFR, KIT, FLT3, FGFR1 and RET, these compounds inhibit tumor cell proliferation and angiogenesis (Table 2) [33][34][35]. 26 May 2020 * Among these RTK inhibitors are included inhibitors of hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL.…”

“…At the moment, four molecular tests are commercially available in the USA to diagnose and evaluate RR for TCs. Principally, each single test is able to detect BRAF as well as molecular alterations of RET on FNA samples [18,34]. Despite this, partial information is available on the effectiveness of molecular tests for cytopathology diagnosis of TCs.…”

“…Several molecules have been correlated with the occurrence of TCs on histopathological samples [15,34]. The expressions of c-met, HGF, P53 isoforms and IL-6 in PTC appear as suitable BMs to recognize cancerous cells [38][39][40][41].…”

Immunohistochemical Profile of Parathyroid Tumours: A Comprehensive Review

“…Thus, immunohistochemistry has become a reasonable adjunct in pathology. For instance, the clinical significance of immunohistochemical surrogate tests in breast carcinoma is similar to gene expression profiling-defined molecular classification [26][27][28]; immunohistochemistry is studied as a substitute for molecular subtyping of gliomas [29,30] and develops as next-generation immunohistochemistry for detection of genetic alterations via evaluation of certain proteins [31].…”