Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma.

Abstract

Background: The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). The aim of this study is to analyze the clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry (IHC) and BRAF RNA in situ hybridization (ISH) in PTC. Methods: This study included 467 patients with PTC who underwent surgical resection. We studied the BRAFV600E mutation using real-time PCR and BRAF V600E and BRAF RNA ISH using tissue microarray (TMA). Results: The frequencies of a positive BRAFV600E mutation by real-time PCR, positive BRAF V600E IHC, and high BRAF RNA ISH were 84%, 86%, and 70%, respectively, in PTC. Conventional PTC had higher positive rates in all three tests than other histologic types. The BRAFV600E mutation, BRAF V600E IHC, low δCt, and high BRAF RNA ISH were significantly associated with lymph node metastasis. The BRAFV600E mutation was significantly associated with positive immunostaining for BRAF V600E mutant protein (P<0.001) overall, with high BRAF RNA ISH only in the follicular variant (P=0.035). No significant correlation was noted between BRAF V600E IHC and BRAF RNA ISH. The sensitivity of BRAF V600E IHC for the BRAFV600E mutation was 95%, and the specificity was 61% overall, 96% and 54% in the conventional type, and 85% and 70% in the follicular variant. Conclusions: Our results showed that positive BRAF V600E IHC significantly correlated with the BRAFV600E mutation. This suggests its clinical utility as a screening tool for the BRAFV600E mutation. In addition, a high BRAF RNA ISH score could be a candidate marker of aggressive behavior in BRAFV600E mutation-positive cases of PTC.