Relationship Between Epstein–Barr Virus LMP-1 and BRAF-V600E Mutant Protein Expression in Ameloblastoma

Abstract

Background: Epstein–Barr virus (EBV) enters the human body via saliva. EBV-encoded latent membrane protein-1 (LMP-1) activates the mitogen-activated protein kinase (MAPK) pathway. MAPK signaling pathway activation due to the BRAF-V600E mutation is widely known as a major event in the pathogenesis of ameloblastoma. It is unclear whether EBV infects ameloblastoma and is involved in the pathogenesis of ameloblastoma. We investigated the relationship between LMP-1 and BRAF-V600E mutant protein expression in ameloblastoma by immunohistochemistry. Methods: We examined a total of 334 samples (ameloblastoma 117 samples, odontogenic keratocyst 127 samples, dentigerous cysts 45 samples, and dental follicle 45 samples). Ephrin type-A receptor 2 (EphA2), BRAF-V600E mutant protein, and γH2AX expression were confirmed by immunohistochemistry. We confirmed that the positive cases of BRAF-V600E mutant protein and γH2AX segregated based on LMP-1 expression: high grade (HG) and low grade (LG). Results: EphA2 expression was high in all lesions. The positive rate of BRAF-V600E mutant protein expression was significantly higher in ameloblastoma, and the positive rate of BRAF-V600E mutant protein in LMP-1 HG cases (71.9%) was significantly greater than in LG cases (39.6%) in ameloblastoma. The positive rate of γH2AX expression was significantly higher in ameloblastoma than in the other lesions. The positive rate of BRAF-V600E mutant protein in LMP-1 HG cases (71.9%) was significantly greater than in LG cases (39.6%) in ameloblastoma. Conclusions: BRAF-V600E mutant protein and γH2AX expression in ameloblastoma were significantly higher in LMP-1 HG cases than in LG cases.