Clinical Oral Investigations

, Volume 23, Issue 2, pp 779–784 | Cite as

Immunohistochemical analysis of BRAF V600E mutation in ameloblastomas

  • Alan Motta do Canto
  • Barbara Michaela Reis da Silva Marcelino
  • Juliana Lucena Schussel
  • Bruna F. Wastner
  • Laurindo Moacir Sassi
  • Luciana Corrêa
  • Ronaldo Rodrigues de Freitas
  • Bengt Hasséus
  • Göran Kjeller
  • Celso Augusto Lemos Junior
  • Paulo Henrique Braz-SilvaEmail author
Original Article



This study aimed to investigate the presence of BRAF V600E mutation in mandible ameloblastomas by correlating clinical and imaging data on the cases studied.


Eighty-four cases diagnosed as mandibular ameloblastoma were selected for analysis. The specimens were submitted to immunohistochemistry for detection of BRAF V600E mutated protein. Clinical-pathological data such as age, gender, tumour size, mandibular location, radiographic aspects, histological type and sub-type, and tumour status were collected. The clinical-pathological parameters were categorised and analysed according to BRAF V600E detection.


Of the 84 patients, 78.6% (66 cases) demonstrated positivity for anti-BRAF V600E antibody, whereas 18 were negative (21.4%). The correlation between BRAF expression and variables showed statistical significances for mandibular location (P = 0.0353) and tumour size (P = 0.008), whereas no statistical significance was observed for gender, age, radiographic aspect, histological pattern, histological sub-type and tumour status. Multivariate logistic regression revealed a significant risk for BRAF positivity in tumours with posterior mandibular location (OR = 7.23, P = 0.0451) and size > 4 cm (OR = 7.29, P = 0.0150).


BRAF V600E mutation is common in mandibular ameloblastomas, especially in cases of tumours larger than 4 cm and in the posterior region of the mandible. In addition, this mutation can occur regardless of histological type of the tumour, age, gender, radiographic aspect and tumour status.

Clinical significance

The association between clinical-pathologic features and BRAF V600E mutation in ameloblastomas may provide directions for the treatment of this neoplasia. The use of BRAF inhibitors for targeted therapy could lead to an establishment of an alternative compared to the resective surgery.


Ameloblastoma Odontogenic tumours Jaw Immunohistochemistry BRAFV600E mutation 



This study was supported by the Government of Brazil through the National Council for Technological Development (CNPq) according to protocol number 443004/2014-5 and São Paulo State Research Support Foundation (FAPESP) according to protocol number 2015/07727-9.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All the procedures performed in our study were in accordance with the ethical standards for human research set by institutional and/or national research committees and with the 1964 Helsinki declaration, including its later amendments or comparable ethical standards. This study was approved by the Research Ethics Committee for Analysis of Research Project under protocol number (1.664.742).


  1. 1.
    Kurppa KJ, Catón J, Morgan PR, Ristimäki A, Ruhin B, Kellokoski J, Elenius K, Heikinheimo K (2014) High frequency of BRAF V600E mutations in ameloblastoma. J Pathol 232:492–498CrossRefPubMedGoogle Scholar
  2. 2.
    McClary AC, West RB, McClary AC, Pollack JR, Fischbein NJ, Holsinger CF, Sunwoo J, Colevas AD, Sirjani D (2016) Ameloblastoma: a clinical review and trends in management. Eur Arch Otorhinolaryngol 273:1649–1661CrossRefPubMedGoogle Scholar
  3. 3.
    Tan S, Pollack JR, Kaplan MJ, Colevas AD, West RB (2016) BRAF inhibitor treatment of primary BRAF-mutant ameloblastoma with pathologic assessment of response. Oral Surg Oral Med Oral Pathol Oral Radiol 122:e5–e7CrossRefPubMedGoogle Scholar
  4. 4.
    Brown NA, Rolland D, McHugh JB, Weigelin HC, Zhao L, Lim MS, Elenitoba-Johnson KS, Betz BL (2014) Activating FGFR2-RAS-BRAF mutations in ameloblastoma. Clin Cancer Res 20:5517–5526CrossRefPubMedGoogle Scholar
  5. 5.
    Sweeney RT, McClary AC, Myers BR, Biscocho J, Neahring L, Kwei KA, Qu K, Gong X, Ng T, Jones CD, Varma S, Odegaard JI, Sugiyama T, Koyota S, Rubin BP, Troxell ML, Pelham RJ, Zehnder JL, Beachy PA, Pollack JR, West RB (2014) Identification of recurrent SMO and BRAF mutations in ameloblastomas. Nat Genet 46:722–725CrossRefPubMedGoogle Scholar
  6. 6.
    Heikinheimo K, Kurppa KJ, Elenius K (2015) Novel targets for the treatment of ameloblastoma. J Dent Res 94:237–240CrossRefPubMedGoogle Scholar
  7. 7.
    Cantwell-Dorris ER, O’Leary JJ, Sheils OM (2011) BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther 10:385–394CrossRefPubMedGoogle Scholar
  8. 8.
    Wright JM, Vered M (2017) Update from the 4th edition of the World Health Organization classification of head and neck tumours: odontogenic and maxillofacial bone tumors. Head Neck Pathol 11:68–77CrossRefPubMedGoogle Scholar
  9. 9.
    do Canto AM, Rozatto JR, Schussel JL, de Freitas RR, Hasséus B, Braz-Silva PH (2016) Immunohistochemical biomarkers in ameloblastomas. Acta Odontol Scand 74:585–590CrossRefPubMedGoogle Scholar
  10. 10.
    Fregnani ER, Perez DE, Paes de Almeida O, Fonseca FP, Soares FA, Castro-Junior G, Alves FA (2017) BRAF-V600E expression correlates with ameloblastoma aggressiveness. Histopathology 70:473–484CrossRefPubMedGoogle Scholar
  11. 11.
    Diniz MG, Gomes CC, Guimarães BV, Castro WH, Lacerda JC, Cardoso SV, de Faria PR, Dias FL, Eisenberg AL, Loyola AM, Gomez RS (2015) Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours. Tumour Biol 36:5649–5653CrossRefPubMedGoogle Scholar
  12. 12.
    Carlson ER, Marx RE (2006) The ameloblastoma: primary, curative surgical management. J Oral Maxillofac Surg 64:484–494CrossRefPubMedGoogle Scholar
  13. 13.
    Kaye FJ, Ivey AM, Drane WE, Mendenhall WM, Allan RW (2014) Clinical and radiographic response with combined BRAF-targeted therapy in stage 4 ameloblastoma. J Natl Cancer Inst 107:378CrossRefPubMedGoogle Scholar
  14. 14.
    Kennedy WR, Werning JW, Kaye FJ, Mendenhall WM (2016) Treatment of ameloblastoma and ameloblastic carcinoma with radiotherapy. Eur Arch Otorhinolaryngol 273:3293–3297CrossRefPubMedGoogle Scholar
  15. 15.
    Gültekin SE, Aziz R, Heydt C, Sengüven B, Zöller J, Safi AF, Kreppel M, Buettner R (2018) The landscape of genetic alterations in ameloblastomas relates to clinical features. Virchows Arch 472:807–814. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alan Motta do Canto
    • 1
    • 2
  • Barbara Michaela Reis da Silva Marcelino
    • 1
  • Juliana Lucena Schussel
    • 3
    • 4
  • Bruna F. Wastner
    • 4
  • Laurindo Moacir Sassi
    • 4
  • Luciana Corrêa
    • 1
  • Ronaldo Rodrigues de Freitas
    • 2
  • Bengt Hasséus
    • 5
  • Göran Kjeller
    • 6
  • Celso Augusto Lemos Junior
    • 7
  • Paulo Henrique Braz-Silva
    • 1
    • 8
    Email author
  1. 1.Department of Stomatology, Division of General Pathology, School of DentistryUniversity of São PauloSão PauloBrazil
  2. 2.Unit of Oral and Maxillofacial Surgery, School of Medical SciencesIrmandade Santa Casa de São PauloSão PauloBrazil
  3. 3.Department of StomatologyFederal University of ParanáCuritibaBrazil
  4. 4.Department of Oral and Maxillofacial SurgeryErasto Gaertner HospitalCuritibaBrazil
  5. 5.Department of Oral Medicine and Pathology, Institute of Odontology, The Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
  6. 6.Department of Oral and Maxillofacial Surgery, Institute of Odontology, The Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
  7. 7.Department of Stomatology, Division of Clinical Stomatology, School of DentistryUniversity of São PauloSão PauloBrazil
  8. 8.Laboratory of Virology, Institute of Tropical Medicine of São PauloUniversity of São PauloSão PauloBrazil

Personalised recommendations