Overexpression of FGFR2 in Mandibular Ameloblastoma Is Potentially Associated with Gene Amplification and Deletion

Ameloblastoma (AM) is a common locally invasive benign odontogenic tumor in Asian populations. Although fibroblast growth factor receptor 2 (FGFR2) mutations have been reported in AM, FGFR2 amplification, the predominant form of FGFR2 aberration in human cancers, remains unexplored. This study aimed to evaluate FGFR2 protein expression, FGFR2 gene copy number variations, and their associations with demographic and clinico-radio-pathological parameters in mandibular AM. Eighty-seven cases of mandibular AM and 10 dental follicle (DF) specimens were included. FGFR2 protein expression was assessed by immunohistochemistry, and gene copy number variations were analyzed using the quantitative real-time polymerase chain reaction (qPCR) technique. Clinical data, including age, gender, tumor size, radiographic features, histological subtype, and recurrence history, were examined for associations with FGFR2 alterations. FGFR2 protein overexpression was observed in 95.4% of AM cases and was not significantly associated with demographic or clinico-radio-pathological variables. FGFR2 gene amplification was detected in 52.5% of cases, while 8.2% showed gene deletion. Notably, 50.8% of cases exhibited concurrent FGFR2 amplification and overexpression, and all cases with FGFR2 gene deletion also demonstrated FGFR2 overexpression. These findings suggest that FGFR2 gene amplification and deletion may contribute to FGFR2 overexpression and play a significant role in the molecular pathogenesis of mandibular AM.