INCREASED SOX2-POSITIVE CELLS IN BRAF(V600E) MUTATED AMELOBLASTOMAS

Abstract

Objective SRY related HMG box gene 2 (SOX2) is a transcription factor expressed in embryonic and adult stem cells. SOX2 positive dental epithelial stem cells have been shown to give rise to all dental epithelial cell lineages. Increased SOX2 expressing cells has been reported in ameloblastic carcinomas than ameloblastomas, which might indicate SOX2 contributes to the pathogenesis of ameloblastic neoplasms. Recent and our previous studies have shown high frequency of BRAF(V600E) mutation in ameloblastomas. Interestingly, recent studies have reported that BRAF mutation is associated with the expression of SOX2 in colorectal cancers. Here, we investigated if SOX2-positive cell component is expanded in BRAF(V600E) mutated than wild type ameloblastomas. Methods Fifty-five formalin fixed paraffin embedded ameloblastoma tissue sections were used for macro-dissection of tumor component, DNA extraction and SOX2 immunohistochemistry. Sanger sequencing was further performed to detect the BRAF(V600E) mutation. The correlation between SOX2 positive cell numbers and BRAF status in ameloblastomas was evaluated by T-test. Results Among 55 ameloblastoma cases, forty-eight cases harbored BRAF(V600E) mutation. SOX2 positive cells were found in all cases regardless of BRAF status with average 22.3% SOX2 positive cells in ameloblastomas. BRAF(V600E) mutated ameloblastoma cases showed significantly more Sox2-positive cells (24.5%) than in wild type (6.6%) (p Conclusion SOX2 positive cells were found in all ameloblastomas and BRAF(V600E) mutated ameloblastomas showed significantly more SOX2-positive cells. The results suggested BRAF(V600E) mutation may contribute to the expansion of SOX2 positive cell compartment.