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Frequency of BRAF V600E mutation in a group of Thai patients with ameloblastomas

      Objective

      BRAF V600E mutation has recently been reported in a high proportion of ameloblastomas. This study was conducted to investigate the frequency of this mutation in ameloblastoma and unicystic ameloblastoma. The correlation between clinicopathologic data and BRAF V600E mutation was also analyzed.

      Study Design

      A total of 51 archival samples of ameloblastomas and 22 cases of unicystic ameloblastomas were examined for BRAF V600E mutation by using anti-BRAF V600E (clone VE1) immunohistochemistry.

      Results

      Positivity for anti-BRAF V600E antibody was detected in 72.5% (37 of 51) of ameloblastomas, but the mutation showed no significant correlation with the clinicopathologic parameters. With regard to unicystic ameloblastoma, 95.5% (21) of the 22 cases exhibited positive immunostaining for BRAF V600E, whereas only 1 case showed the mural subtype of wild-type BRAF.

      Conclusions

      A high frequency of BRAF V600E mutation was detected in a group of Thai patients with ameloblastomas, suggesting the future use of BRAF-targeted therapy in patients with BRAF-mutated ameloblastoma. However, no significant association between BRAF V600E mutation and the clinicopathologic characteristics of ameloblastomas was found in our study.
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      References

        • Dhanuthai K.
        • Chantarangsu S.
        • Rojanawatsirivej S.
        • et al.
        Ameloblastoma: a multicentric study.
        Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 113: 782-788
      1. El-Naggar A. Chan J. Grandis J. Takata T. Slootweg P. WHO Classification of Head and Neck Tumours. IARC Press, Lyon, France2017
        • Ladeinde A.L.
        • Ogunlewe M.O.
        • Bamgbose B.O.
        • et al.
        Ameloblastoma: analysis of 207 cases in a Nigerian teaching hospital.
        Quint Int (Berlin, Germany). 2006; 37: 69-74
        • Ackermann G.L.
        • Altini M.
        • Shear M.
        The unicystic ameloblastoma: a clinicopathological study of 57 cases.
        J Oral Pathol. 1988; 17: 541-546
        • McClary A.C.
        • West R.B.
        • McClary A.C.
        • et al.
        Ameloblastoma: a clinical review and trends in management.
        Eur Arch Oto-Rhino-Laryngol. 2016; 273: 1649-1661
        • Kurppa K.J.
        • Caton J.
        • Morgan P.R.
        • et al.
        High frequency of BRAF V600E mutations in ameloblastoma.
        J Pathol. 2014; 232: 492-498
        • Brown N.A.
        • Rolland D.
        • McHugh J.B.
        • et al.
        Activating FGFR2-RAS-BRAF mutations in ameloblastoma.
        Clin Cancer Res. 2014; 20: 5517-5526
        • Heikinheimo K.
        • Kurppa K.J.
        • Elenius K.
        Novel targets for the treatment of ameloblastoma.
        J Dent Res. 2015; 94: 237-240
        • Kelppe J.
        • Thoren H.
        • Ristimaki A.
        • Haglund C.
        • Sorsa T.
        • Hagstrom J.
        BRAF V600E expression in ameloblastomas—a 36-patient cohort from Helsinki University Hospital.
        Oral Dis. 2019; 25: 1169-1174
        • do Canto A.M.
        • da Silva Marcelino B.M.R.
        • Schussel J.L.
        • et al.
        Immunohistochemical analysis of BRAF V600E mutation in ameloblastomas.
        Clin Oral Investig. 2019; 23: 779-784
        • Diniz M.G.
        • Gomes C.C.
        • Guimaraes B.V.
        • et al.
        Assessment of BRAF V600E and SMO F412 E mutations in epithelial odontogenic tumours.
        Tumour Biol. 2015; 36: 5649-5653
        • Safaee Ardekani G.
        • Jafarnejad S.M.
        • Tan L.
        • Saeedi A.
        • Li G.
        The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis.
        PloS One. 2012; 7: e47054
        • Wang Z.
        • Chen J.Q.
        • Liu J.L.
        • Qin X.G.
        Clinical impact of BRAF mutation on the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta-analysis.
        Eur J Clin Investig. 2016; 46: 146-157
        • Santarpia L.
        • Lippman S.M.
        • El-Naggar A.K.
        Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy.
        Exp Opin Ther Targets. 2012; 16: 103-119
        • Tan S.
        • Pollack J.R.
        • Kaplan M.J.
        • Colevas A.D.
        • West R.B.
        BRAF inhibitor treatment of primary BRAF-mutant ameloblastoma with pathologic assessment of response.
        Oral Surg Oral Med Oral Pathol Oral Radiol. 2016; 122: e5-e7
        • Fernandes G.S.
        • Girardi D.M.
        • Bernardes J.P.G.
        • Fonseca F.P.
        • Fregnani E.R.
        Clinical benefit and radiological response with BRAF inhibitor in a patient with recurrent ameloblastoma harboring V600E mutation.
        BMC Cancer. 2018; 18: 887
        • Capper D.
        • Preusser M.
        • Habel A.
        • et al.
        Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody.
        Acta Neuropathol. 2011; 122: 11-19
        • Fregnani E.R.
        • Perez D.E.
        • Paes de Almeida O.
        • et al.
        BRAF-V600E expression correlates with ameloblastoma aggressiveness.
        Histopathology. 2017; 70: 473-484
        • Guan P.
        • Wong S.F.
        • Lim J.Q.
        • et al.
        Mutational signatures in mandibular ameloblastoma correlate with smoking.
        J Dent Res. 2019; 98: 652-658
        • Oh K.Y.
        • Cho S.D.
        High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: clinicopathological significance and correlation with epithelial-mesenchymal transition.
        J Oral Pathol Med. 2019; 48: 413-420
        • Bartels S.
        • Adisa A.
        • Aladelusi T.
        • et al.
        Molecular defects in BRAF wild-type ameloblastomas and craniopharyngiomas—differences in mutation profiles in epithelial-derived oropharyngeal neoplasms.
        Virchows Arch. 2018; 472: 1055-1059
        • Shirsat P.M.
        • Bansal S.
        • Prasad P.
        • Desai R.S.
        Low frequency of BRAF V600E immunoexpression in mandibular ameloblastomas: an institutional study.
        J Oral Maxillofac Pathol. 2018; 22: 353-359
        • Sweeney R.T.
        • McClary A.C.
        • Myers B.R.
        • Biscocho J.
        • Neahring L.
        Identification of recurrent SMO and BRAF mutations in ameloblastomas.
        Nat Genet. 2014; 46: 722-725
        • Pereira N.B.
        • Pereira K.M.
        • Coura B.P.
        • et al.
        BRAF V600E mutation in the diagnosis of unicystic ameloblastoma.
        J Oral Pathol Med. 2016; 45: 780-785
        • Kaye F.J.
        • Ivey A.M.
        • Drane W.E.
        • Mendenhall W.M.
        • Allan R.W.
        Clinical and radiographic response with combined BRAF-targeted therapy in stage 4 ameloblastoma.
        J Natl Cancer Inst. 2015; 107: 378
        • Faden D.L.
        • Algazi A.
        Durable treatment of ameloblastoma with single agent BRAFi Re: clinical and radiographic response with combined BRAF-targeted therapy in stage 4 ameloblastoma.
        J Natl Cancer Inst. 2017; 109: djw190