MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration.
OBJECTIVE
MicroRNAs (miRNAs) are small endogenous noncoding RNAs that pair with target messengers regulating gene expression. Changes in miRNA levels occur in thyroid cancer. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytological diagnosis remains undetermined for 20% of nodules.


METHODS
In this study, we evaluated the expression of seven miRNAs in benign nodules, papillary thyroid carcinomas (PTCs), and undetermined nodules at FNA.


METHODS
The 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.


RESULTS
Using 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 six false-negative predictions. The mutated form V600E of BRAF gene was demonstrated in 19/43 PTCs and in 1/53 undetermined nodules.


CONCLUSIONS
The expression profiles of three miRNAs allowed us 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.
Department of Endocrinology, Research Center of Excellence AmbiSEN, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.
Patrizia
P
Agretti
Eleonora
E
Ferrarini
Teresa
T
Rago
Antonio
A
Candelieri
Giuseppina
G
De Marco
Antonio
A
Dimida
Filippo
F
Niccolai
Angelo
A
Molinaro
Giancarlo
G
Di Coscio
Aldo
A
Pinchera
Paolo
P
Vitti
Massimo
M
Tonacchera
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D044963:Biopsy, Fine-Needle; D002277:Carcinoma; D002291:Carcinoma, Papillary; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011446:Prospective Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016606:Thyroid Nodule / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D014408:Biomarkers, Tumor; D035683:MicroRNAs