BRAF V600E mutation and microRNAs are helpful in distinguishing papillary thyroid malignant lesions: Tissues and fine needle aspiration cytology cases

Aims: Mutations of BRAF oncogene are considered to contribute in the invasiveness and poor clinicopathologic features of papillary thyroid cancer (PTC). As a step towards understanding the underlying molecular mechanisms of this contribution, we aimed to examine the association of four microRNAs' (miR-222, -137, -214, -181b) levels with BRAFV600E and clinicopathological features in PTC tissues and fine needle aspiration (FNA) specimens. Methods: In total, 56 PTC and 27 benign with multinodular goiter tissue samples, 95 FNA samples, and B-CPAP and HEK293 cell lines were examined. BRAFV600E mutation was examined in PTC tissues and FNA samples. Expression of microRNAs was assessed by real-time quantitative reverse transcription-PCR. Key findings: The frequency of BRAFV600E in PTC tissues and FNA samples suspicious for PTC was 41.1 and 36.8%, respectively. MiR-222, -137, -214, and -181b were significantly upregulated in PTC tumors (P < 0.05) and in B-CPAP cell line (P < 0.001). In FNA, the expressions of miR-222, -181b and -214 were significantly elevated in patients suspected for PTC (P < 0.05), while there was no significant difference in miR-137. After adjustment for age and sex, miR-181b was associated with an increased risk of bearing BRAFV600E mutation (OR: 1.27; 95% CI: 1.01-1.61; P = 0.045) and risk of lymphovascular invasion (OR: 1.66; 95% CI: 1.01-2.72; P = 0.045); miR-137 was associated with the risk of larger tumor size (OR: 1.31; 95% CI: 1.04-1.65; P = 0.022); miR-222 was related to increase in extracapsular invasion (OR: 1.28; 95% CI: 1.04-1.57; P = 0.018). Significance: Upregulation of miR-222, -214 and -181b has been confirmed in PTC tumors, FNA samples and cell line. MiR-137 upregulation has been confirmed in PTC tumors and cell line, but not in FNA samples. MiR-222, -137 and -181b showed an association with the degree of malignancy in PTC tumors.