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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). BRAFV600E 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 BRAFV600E 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, BRAFV600E mutation was identified in 19/23 (82.6%) mandibular ameloblastomas and 0/7 (0.0%) maxillary ameloblastomas. BRAFV600E 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 BRAFV600E mutation is considerably less frequent.

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Fig. 1: Summary of clinicopathologic, immunohistochemical, and molecular findings in ameloblastoma.
Fig. 2: BRAF VE1 immunopositivity in unicystic ameloblastoma.
Fig. 3: Variant BRAF VE1 immunopositivity in ameloblastoma.
Fig. 4: BRAF VE1 immunoreactivity in histologic variants of ameloblastoma.
Fig. 5: BRAF VE1 immunonegativity in KCOT/DC and equivocal immunoreactivity in ameloblastoma.

Data availability

All data generated or analyzed during this study are included in this published article.


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We thank Mr. Amad Awadallah and Mr. Cameron Norris for their excellent technical assistance. This work was supported by University Hospitals Cleveland Medical Center, Department of Pathology intradepartmental funds.

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Authors and Affiliations



L.D.M. and I.J.S. performed study concept and design and wrote the paper. S.L.A., J.W. and I.J.S. performed pathological and immunohistochemical review of the cases. L.D.M., N.S.W. and I.J.S. acquired clinicopathologic data. J.M.Y. performed acquisition and interpretation of molecular data. All authors read and approved the final paper.

Corresponding author

Correspondence to Ivan J. Stojanov.

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The authors declare no competing interests.

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The present study was approved by the Institutional Review Board of University Hospitals Cleveland Medical Center (STUDY20200628) and conducted in accordance with the Declaration of Helsinki.

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Mendez, L.D., Wolsefer, N.S., Asa, S.L. et al. The diagnostic utility of BRAF VE1 mutation-specific immunohistochemistry in ameloblastoma. Mod Pathol (2022).

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