Clinical significance of BRAF V600E mutation in 154 patients with thyroid nodules.

The aim of the present study was to investigate the prevalence of the BRAF V600E mutation in papillary thyroid carcinoma (PTC) patients from eastern coastal China and to determine whether it is correlated with the clinicopathological features of PTCs with or without current Hashimoto thyroiditis (HT). The BRAF V600E mutation status was analyzed in 206 thyroid nodules of 154 patients undergoing thyroidectomy using polymerase chain reaction and bi-directional sequencing. Multivariate analysis was performed to investigate the association of the BRAF V600E mutation with clinicopathological features. Thyroid nodules were classified as PTC, nodular goiter (NG), adenomatoid nodule, adenoma and HT. The BRAF V600E mutation was observed in 61.5% of PTCs analyzed; it was also detected in one normal tissue adjacent to PTC and one NG. One patient exhibited double mutations in the BRAF gene; the BRAF V600E mutation in the PTC lesion and the BRAF K601E mutation in the contralateral NG lesion. Patients harboring the BRAF V600E mutation had higher thyroid stimulating hormone levels (2.453±1.464 vs. 1.966±1.296 mIU/l), a reduced occurrence of papillary thyroid microcarcinoma (55.0 vs. 88%), and a higher occurrence of lymph node metastasis (LNM; 42.5 vs. 16.0%) compared with those with wild-type BRAF (all P<0.05). Binary logistic regression analysis revealed that the BRAF V600E mutation was associated with LNM of PTC (hazard ratio, 5.051; 95% confidence interval, 1.068-23.893; P=0.041). Conversely, no association was identified between the BRAF V600E mutation and HT (38.5 vs. 67.3%, χ2=3.656, P=0.056). Thus, in regional PTCs, the BRAF V600E mutation was prevalent, suggesting that it may be an early and phenotypically defining molecular event in PTC, and may represent an independent factor that predicts LNM.