The diagnostic utility of BRAF VE1 mutation-specific immunohistochemistry in ameloblastoma

Ameloblastoma is a benign, locally aggressive odontogenic neoplasm with variable solid and cystic morphology. On account of its histologic variety, diagnostically challenging cases can bear resemblance to odontogenic keratocyst/keratocystic odontogenic tumor (KCOT) or dentigerous cyst (DC). BRAF(V600E) mutation has been reported to be specific for and frequent in ameloblastoma, and this study evaluated the usefulness of immunohistochemistry (IHC) using the BRAF VE1 mutant-specific antibody as a diagnostic adjunct in this setting. We investigated 46 ameloblastomas, 30 KCOTs, and 30 DCs. BRAF VE1 IHC was performed on all cases and allele-specific polymerase chain reaction (AS-PCR) for BRAF(V600E) mutation was performed on 30 ameloblastomas and any IHC-positive KCOT/DC. BRAF VE1 IHC was positive in 31/37 (83.8%) mandibular ameloblastomas but not in any maxillary ameloblastomas (0/9), KCOT (0/30), or DC (0/30). Equivocal staining was seen in 1/37 (3.3%) mandibular ameloblastomas. Of the 30 ameloblastomas subjected to AS-PCR, BRAF(V600E) mutation was identified in 19/23 (82.6%) mandibular ameloblastomas and 0/7 (0.0%) maxillary ameloblastomas. BRAF(V600E) mutant ameloblastomas were positive by IHC in 18/19 (94.7%) cases and equivocal in 1/19 (5.3%) cases. All 11 (100.0%) BRAF-wild type ameloblastomas were negative by IHC. BRAF VE1 is an excellent tool for the diagnosis of mandibular ameloblastoma but of limited utility in the maxilla, where it less commonly occurs and where BRAF(V600E) mutation is considerably less frequent.

Automated summary

This study evaluated the usefulness of immunohistochemistry (IHC) using the BRAF VE1 mutant-specific antibody as a diagnostic adjunct in mandibular ameloblastoma. The study found that the BRAF(V600E) mutation is more frequent in mandibular ameloblastoma and less frequent in maxillary ameloblastoma. BRAF VE1 IHC is a highly accurate tool for the diagnosis of mandibular ameloblastoma.