High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: Clinicopathological significance and correlation with epithelial-mesenchymal transition.

Abstract

BRAF V600E mutations are activating mutations that have recently been detected in ameloblastoma. However, their prevalence has not been reported in East Asian patients with ameloblastoma and their clinicopathological significance remains unclear. In this study, we examined the prevalence and clinicopathological significance of BRAF V600E mutations in Korean patients with ameloblastoma. In addition, we investigated the relationship between BRAF V600E mutations and epithelial-mesenchymal transition, which has not been studied in ameloblastoma. Thirty ameloblastoma tissue samples were collected, and DNA isolation, polymerase chain reaction, and Sanger sequencing were performed to detect BRAF V600E mutations. Immunohistochemistry was carried out using antibodies against two epithelial-mesenchymal transition-inducing transcription factors, Twist and Snail. Associations of BRAF V600E mutations with clinicopathological factors and expression of Twist and Snail were statistically analyzed. We found a high frequency (90.0%) of BRAF V600E mutations, and mutation status was not associated with clinicopathological factors including age, tumor location, and recurrence. Positive expression of Twist and Snail was observed in 33.3% and 56.7% of cases, respectively, and associated with recurrence (P=0.020 and 0.010, respectively). There was no correlation between BRAF V600E mutation status and expression of Twist and Snail (P=1.000, for both). A higher prevalence of BRAF V600E mutations was identified in Korean patients with ameloblastoma compared with previous studies, which indicates that BRAF-targeted therapies can be widely used for refractory ameloblastomas. Furthermore, our findings suggest that BRAF V600E mutations and epithelial-mesenchymal transition may act independently in the development of ameloblastoma.