MicroRNA EXPRESSION PROFILE HELPS TO DISTINGUISH BENIGN NODULES FROM PAPILLARY THYROID CARCINOMAS STARTING FROM CELLS OF FINE NEEDLE ASPIRATION.

摘要

OBJECTIVE:\ud\udMicroRNAs (miRNAs) are small endogenous non-coding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules.\ud\udDESIGN:\ud\udIn this study we evaluated the expression of 7 miRNAs in benign nodules, papillary thyroid carcinomas (PTC) and undetermined nodules at FNA.\ud\udMETHODS:\ud\udThe prospective study included 141 samples obtained by FNA of thyroid nodules from 138 patients. miRNA expression was evaluated by quantitative RT-PCR and statistical analysis of data was performed. Genetic analysis of codon 600 of BRAF gene was also performed.\ud\udRESULTS:\ud\udUsing data mining techniques we obtained a criterion to classify a nodule as benign or malignant on the basis of miRNA expression. The decision model based on the expression of miR-146b, miR-155 and miR-221 was valid for 86/88 nodules with determined cytology (97.73%), and adopting cross-validation techniques we obtained a reliability of 78.41%. The prediction was valid for 31/53 undetermined nodules with 16 false positive and 6 false negative predictions. The mutated form V600E of BRAF gene was demonstrated in 19/43 PTCs and in 1/53 undetermined nodules.\ud\udCONCLUSIONS:\ud\udThe expression profiles of three miRNAs allowed to distinguish benign from PTC starting from FNA. When the assay was applied to discriminate thyroid nodules with undetermined cytology a low sensitivity and specificity despite the low number of false negative predictions was obtained, limiting the practical interest of the method.