Endocrine Abstracts

Introduction: Several studies recommend the use of molecular tests for a complete diagnosis of malignancy in thyroid carcinomas (TC). The study and identification of molecular markers in thyroid will contribute to a personalized and effective treatment of the patients. The development of TC has been associated with the activation of oncogenes that are implicated in the cell signaling pathway, interfering in cancer promotion and outcome. Moreover, the repertoire of microRNAs (miRNAs) in TC has been recently identified as being important in tumor development and progression. The assessment of miRNAs expression represents a promising area of study in cancer.

Aims: This study aims to evaluate the role of miRNAs (miR146b, miR221, miR222 and miR15a) expression and the molecular association with genetic alterations (TERTp, BRAF and RAS (NRAS, HRAS and KRAS)) in the improvement of differentiated thyroid cancer (DTC) diagnosis.

Material and methods: For the relative quantification of miRNAs expression, a total of 83 thyroid samples, composed by formalin-fixed paraffin embedded (FFPE) samples of 12 benign and 71 malignant tumors (DTC) were selected. MicroRNA expression was assessed for miR146b, miR221, miR222, and miR15a by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and the results were analyzed using the 2^{- ΔΔCT} method. The discriminative ability of miRNAs expression regarding DTC diagnosis was evaluated using the area under the Receiver Operating Characteristic Curve (AUC). Cut-off values maximizing sensitivity were obtained. The association of miRNAs expression and genetic alterations was evaluated.

Results/Discussion: All four analyzed miRNAs showed a tendency to be over expressed in malignant tumors when compared with benign lesions. Corresponding discriminative abilities regarding DTC diagnosis were: miR146b (AUC 0.81, 95%CI 0.71-0.91), miR221 (AUC 0.74, 95%CI 0.64-0.84), miR15a (AUC 0.77, 95%CI 0.66-0.88), and miR222 (AUC 0.66, 95%CI 0.55-0.77). Cut-offs were 1.05 for miR146b with sensitivity (se) 82.5 and specificity (sp) 66.7, 1.35 for miR221 (se=71.8, sp = 73.3), 1.35 for miR15a (se=72.5, sp = 66.7), and 0.84 for miR222 (se=69.4, sp = 53.3). Our data reveals a significant statistical association between higher expression levels of all miRNAs, but miR15a, with BRAF mutation (P < 0.001), suggesting a connection of this mutation with miRNAs expression, in accordance with other studies. Although this study had a limited sample size, three of the miRNAs showed a good discriminative ability in DTC. The association between the miRNAs profiling and molecular analysis could be useful for an accurate diagnosis of DTCs.