A multi-center cross-sectional investigation of BRAF V600E mutation in Ameloblastoma.
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BACKGROUND: B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation stands as a pivotal genetic alteration strongly associated with several neoplasms and contributes significantly to their pathogenesis as well as potential targeted treatment strategies. OBJECTIVE: This cross-sectional study aimed to determine the frequency of BRAF V600E mutation in ameloblastoma in a multi-center of Thailand. METHOD: Anti-BRAF V600E (clone VE1) immunohistochemistry was performed on 227 conventional ameloblastoma (AM) and 113 unicystic ameloblastoma (UA) samples collected from four major dental schools located in the Central, North, South, and Northeast regions of Thailand. Tumor cells from randomly chosen AM cases were also micro-dissected from the FFPE sections and subjected to DNA sequencing to confirm the immunohistochemical results. RESULTS: BRAF V600E mutation was detected in 71.8% of the AM samples, while 65.5% of samples with UAs demonstrated BRAF V600E positivity. The BRAF V600E mutation was significantly different in the histological subtypes of AMs in the four centers (p = 0.012) and the location of UA in three centers (p = 0.013). There was no significant association between the BRAF V600E mutation and the location of ameloblastoma in the overall prevalence of our multi-center study; nonetheless, a statistically significant association was found between the BRAF V600E mutation and the mandible location of AMs from the Central Faculty of Dentistry, Mahidol University (MU) center (p = 0.033), as well as with the histological subtypes of AMs from the Southern Faculty of Dentistry, Prince of Songkla University (PSU) center (p = 0.009). No statistical association was observed between the BRAF V600E mutation and AM and UA recurrence (p = 0.920 and p = 0.312), respectively. The results of DNA sequencing performed in randomly selected 40 BRAF V600E-positive and 20 BRAF V600E-negative ameloblastoma tissues were in accordance with the immunohistochemical findings. CONCLUSION: As a result of a notable prevalence of BRAF V600E in Thai individuals diagnosed with ameloblastoma, they may benefit from the utilization of adjunctive anti-BRAF targeted therapy for treatment.