The evaluation of miRNAs on thyroid FNAC: the promising role of miR-375 in follicular neoplasms.

Abstract

Fine needle aspiration cytology (FNAC) plays an essential role in the evaluation of thyroid nodules especially for the category of follicular neoplasms (FN) representing 25% of all thyroid cases including different neoplastic entities. Hence, one of the most promising areas is the application of molecular tests to FNAC. Among them, microRNAs (miRNA),identified as negative (post-transcriptional) gene expression regulators involved in tumor development, are likely to discriminate among FNs. Limited data explored the use of miRNAs on FNAC as well as their role in the malignant risk stratification. We aimed to define whether liquid-based cytology (LBC) is a valid method for miRNA evaluation. From June 2014 to March 2015, we enrolled 27FNs with histological follow-up. In the same reference period, 13 benign nodules (BN) and 20 positive for malignancy (PM) were selected as controls. Histologically, FNs resulted in 14 malignancies (3 papillary thyroid carcinoma-PTC and 11 follicular variant of PTC-FVPC) and 13 follicular adenomas (FA). The 20 PMs included two FVPC, 16 PTC and two medullary thyroid carcinoma (MTC). Five miRNAs (10b, 92a, 221/222 cluster, and 375) were studied on LBC and quantified by real-time PCR. Only miR-375 was over-expressed in the FNs diagnosed as carcinomas and in the PMs. A cut-off of 12 miR-375/U6 relative ratio recognized all BNs and 95% PMs. Specifically, in each category, FVPCs and PTCs did not show any difference while MTCs had the highest value. miR-375 shows 97.1% sensitivity, 100% specificity, 96.3% negative predictive value (NPV), 100% positive predictive value (PPV), and 98.3% diagnostic accuracy. LBC is suitable for miRNAs evaluation. miR-375 resulted over-expressed in all malignant FNs and 95% PMs. It may represent a valid aid in ruling out BNs and supporting PTCs and/or FVPCs.