Molecular Biology of Papillary Thyroid Microcarcinomas: What is New?

Objectives: Papillary thyroid microcarcinoma (PTMC), a tumor that measures 1 cm or less, according to World Health Organization (WHO) histological classification of tumors, is the most common form of papillary thyroid carcinoma (PTC) comprising much more than half of all PTCs if one includes the socalled incidentalomas. Although PTMC has an excellent prognosis, a minority of cases were found to be clinically aggressive. We decided to perform a review of the literature on records on PTMC in attempt to find which molecular markers might be used as predictors of the clinical behavior of PTMC. This review article aims to summarize the molecular mechanisms that were associated to PTMCs described in the last 10 years, with a particular focus on the clinical importance of genetic alterations (BRAF mutation, RET/PTC rearrangement, NAD(P)H and NRH polymorphisms and TERT mutation) and anomalous expression of several molecules (P53, P27, COX-2, EGFR, ki-67, S100A4, cyclin Dl, galectin-3, HMWK, CK-19, HBME-1, HGF, c-MET, membrane mucins and cell adhesion molecules). Methods: We made a systematic search in the PubMed database using the keywords papillary thyroid microcarcinoma and reviewed all the articles published in the last 10 years, in English, addressing issues related to PTMC. Results: Unfortunately, all genetic alterations and biomarkers reported to date have little potential per se to differentiate between indolent and aggressive PTMCs. Further studies using the aforementioned markers and, most likely, others are needed in order to try to find a combination of several markers that may be used for increasing the probability of identifying PTMC cases with more aggressive behavior, thus allowing the establishment of a more appropriately targeted treatment. (C) 2016 Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo. Published by Elsevier Espafia, S.L.U.