miRNA expression profiling of Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: more light on its behavior

Follicular variant of PTC (FVPTC) is a variant of well differentiated papillary thyroid carcinoma. FVPTCs comprise encapsulated and infiltrative forms with different histo-logical features and clinical behavior, but according cytomorphological features the forms with indolent behavior are not significant different from those with aggressive phenotype. Since the encapsulated forms with no capsular invasion show an indolent clinical behavior similar to benign lesion, recently , an international panel of patholo-gists and clinicians has reclassified these lesions as a distinct class of thyroid tumors termed as “Non-invasive follicular thyroid neoplasms with papillary-like nuclear fea-tures” (NIFTP). To better classify these tumors by a molecular viewpoint and to evaluate new diagno-stic tool to improve pre-surgical differential diagnosis between NIFTPs, Follicular Adenomas (FAs) and Infiltrative FVPTCs, an expression profiling of 798 miRNAs was performed. miRNA expression levels were detected in 54 thyroid tumors (18 Follicular adeno-mas, 19 NIFTPs and 17 Infiltrative FVPTCs) using an highly reproducible and sensi-tive method, nCounter Nanostring assay. A set of differentially expressed miRNAs was identified. miR-146-5p, miR-221-5p, miR-222-3p, miR-30e-3p and miR-152-3p were able to discriminate benign from ma-lignant lesions with a very high level of significance (p-value<0.001); miR-146-5p, miR-199a-5p, miR-199b-5p, miR-1915-3p and miR-148b-3p were most probably as-sociated with a infiltrative growth of FVPTCs. miR-152-3p, miR-185-5p, miR-574-3p were found to be strongly down-regulated in NIFTPs compared with FAs whereas a significant overexpression of miR-10a-5p was reported in NIFTPs compared with infiltrative forms of FVPTC. In conclusion, our data suggest that a panel of these markers could have a high diag-nostic potential and could be applied in the preoperative assessment of thyroid nodu-les, mainly for the lesions that cannot be reliably distinguished on cytology alone and are classified as indeterminate nodules.