Diagnostic accuracy of a mutation-specific monoclonal antibody (RM8 clone) for BRAF V600e detection by immunohistochemistry in ameloblastomas

Allan Vinícius Martins-de-Barros; Fábio Andrey da Costa Araújo; Ana Maria Ipólito Barros; Raisa Jordana Geraldine Severino Lazo; Adauto Gomes Barbosa Neto; Helker Albuquerque Macedo da Silva; Maria Tereza Cartaxo Muniz; Stefânia Jeronimo Ferreira; Marianne de Vasconcelos Carvalho

doi:10.5327/2525-5711.274

Autores

Allan Vinícius Martins-de-Barros Universidade de Pernambuco, Odontologia, Campus Arcoverde – Arcoverde (PE), Brazil.
Fábio Andrey da Costa Araújo Universidade de Pernambuco, Faculdade de Odontologia, Programa de Pós-Graduação em Odontologia – Recife (PE), Brazil. https://orcid.org/0000-0001-5488-9333
Ana Maria Ipólito Barros Universidade de Pernambuco, Faculdade de Odontologia, Programa de Pós-Graduação em Odontologia – Recife (PE), Brazil. https://orcid.org/0000-0001-6739-0988
Raisa Jordana Geraldine Severino Lazo Universidade de Pernambuco, Faculdade de Odontologia, Programa de Pós-Graduação em Odontologia – Recife (PE), Brazil. https://orcid.org/0000-0003-4963-308X
Adauto Gomes Barbosa Neto Universidade de Pernambuco, Instituto de Ciências Biológicas – Recife (PE), Brazil. https://orcid.org/0000-0002-9545-7905
Helker Albuquerque Macedo da Silva Universidade de Pernambuco, Instituto de Ciências Biológicas – Recife (PE), Brazil. https://orcid.org/0000-0003-3549-893X
Maria Tereza Cartaxo Muniz Universidade de Pernambuco, Instituto de Ciências Biológicas – Recife (PE), Brazil. https://orcid.org/0000-0001-9498-5223
Stefânia Jeronimo Ferreira Universidade de Pernambuco, Odontologia, Campus Arcoverde – Arcoverde (PE), Brazil. https://orcid.org/0000-0001-6656-6435
Marianne de Vasconcelos Carvalho Universidade de Pernambuco, Odontologia, Campus Arcoverde – Arcoverde (PE), Brazil. https://orcid.org/0000-0002-6815-5696

DOI:

https://doi.org/10.5327/2525-5711.274

Palavras-chave:

Ameloblastoma, Immunohistochemistry, BRAF V600E, Monoclonal Antibodies, RM8 clone

Resumo

Objective: To determine the diagnostic accuracy of IHC using anti-BRAF V600E monoclonal antibody (RM8 clone) compared to Real-Time PCR in the detection of BRAF V600E mutation in FFPE ameloblastoma samples. Methods: This is a diagnostic accuracy study conducted based on the STARD recommendations. The index test was the IHC with anti-BRAF V600E antibody (RM8 clone), while the reference standard was the DNA analysis through castPCR™ mutation detection assays. The target condition was the detection of BRAF V600E mutation. The FFPE ameloblastoma samples were independently submitted to index test and reference standard. Sensitivity and specificity measures, and positive and negative predictive values were calculated. Results: Fifty-four FFPE ameloblastoma samples were included. The sensitivity and specificity of IHC using the RM8 clone compared do Real-Time PCR for the detection of the BRAF V600E mutation in FFPE ameloblastoma samples was 1.00 (95% CI: 0.90 - 1.00) and 0.46 (95% CI: 0.21 - 0.73), respectively, and the diagnostic test accuracy was calculated as 85.18%. Conclusion: IHC using BRAF V600E-specific antibody (RM8 clone) showed extremely high sensitivity, but suboptimal specificity when compared with Real-Time PCR in the detection of BRAF V600E mutation in FPPE ameloblastoma samples.

Referências

Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-54. https://doi.org/10.1038/nature00766

Cantwell-Dorris ER, O'Leary JJ, Sheils OM. BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther. 2011;10(3):385-94. https://doi.org/10.1158/1535-7163.MCT-10-0799

World Health Organization. Head and neck tumours. Lyon: International Agency for Research on Cancer; 2022.

Martins-de-Barros AV, Silva CCG, Gonçalves KKN, Almeida RAC, Silva EDO, Araújo FAC, et al. Does BRAF V600E mutation affect recurrence rate of ameloblastomas? Systematic review and meta-analysis. J Oral Pathol Med. 2023;52(8):701-9. https://doi.org/10.1111/jop.13458

Effiom OA, Ogundana OM, Akinshipo AO, Akintoye SO. Ameloblastoma: current etiopathological concepts and management. Oral Dis. 2018;24(3):307-16. https://doi.org/10.1111/odi.12646

Martins-de-Barros AV, Anjos RS, Silva CCG, Silva EDO, Araújo FAC, Carvalho MV. Diagnostic accuracy of immunohistochemistry compared with molecular tests for detection of BRAF V600E mutation in ameloblastomas: systematic review and meta-analysis. J Oral Pathol Med. 2022;51(3):223-30. https://doi.org/10.1111/jop.13278

Loo E, Khalili P, Beuhler K, Siddiqi I, Vasef MA. BRAF V600E mutation across multiple tumor types: correlation between DNA-based sequencing and mutation-specific immunohistochemistry. Appl Immunohistochem Mol Morphol. 2018;26(10):709-13. https://doi.org/10.1097/pai.0000000000000516

Capper D, Preusser M, Schittenhelm J. Characterization of immunohistochemical staining patterns of an antibody specific for BRAF V600E protein in primary and metastatic brain tumors. Clin Neuropathol. 2011;30:254-5.

Brown NA, Rolland D, McHugh JB, Weigelin HC, Zhao L, Lim MS, et al. Activating FGFR2-RAS-BRAF mutations in ameloblastoma. Clin Cancer Res. 2014;20(21):5517-26. https://doi.org/10.1158/1078-0432.ccr-14-1069

Kurppa KJ, Catón J, Morgan PR, Ristimäki A, Ruhin B, Kellokoski J, et al. High frequency of BRAF V600E mutations in ameloblastoma. J Pathol. 2014;232(5):492-8. https://doi.org/10.1002/path.4317

Heikinheimo K, Huhtala JM, Thiel A, Kurppa KJ, Heikinheimo H, Kovac M, et al. The mutational profile of unicystic ameloblastoma. J Dent Res. 2019;98(1):54-60. https://doi.org/10.1177/0022034518798810

Oh K, Cho SD, Yoon HJ, Lee JI, Ahn SH, Hong SD. 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(5):413-20. https://doi.org/10.1111/jop.12851

Marcelino BMRS, Parise GK, Canto AM, Sassi LM, Sarmento DJS, Costa ALF, et al. Comparison of immunohistochemistry and DNA sequencing for BRAF V600E mutation detection in mandibular ameloblastomas. Appl Immunohistochem Mol Morphol. 2021;29(5):390-3. https://doi.org/10.1097/PAI.0000000000000904

Cohen JF, Korevaar DA, Altman DG, Bruns DE, Gatsonis CA, Hooft L, et al. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open. 2016;6(11):e012799. https://doi.org/10.1136/bmjopen-2016-012799

Fregnani ER, Perez DEC, Almeida OP, Fonseca FP, Soares FA, Castro-Junior G, et al. BRAF-V600E expression correlates with ameloblastoma aggressiveness. Histopathology. 2017;70(3):473-84. https://doi.org/10.1111/his.13095

Sweeney RT, McClary AC, Myers BR, Biscocho J, Neahring L, Kwei KA, et al. Identification of recurrent SMO and BRAF mutations in ameloblastomas. Nat Genet. 2014;46(7):722-5. https://doi.org/10.1038/ng.2986

Martins-de-Barros AV, Barros AMI, Lazo RJGS, Barbosa Neto AG, Araújo FAC, Carvalho MV. BRAF V600E mutation detected in cell-free DNA from conventional ameloblastomas fluid aspirate. Oral Dis. 2024;30(6):3962-5. https://doi.org/10.1111/odi.14855

Kaye FJ, Ivey AM, Drane WE, Mendenhall WM, Allan RW. Clinical and radiographic response with combined BRAF-targeted therapy in stage 4 ameloblastoma. J Natl Cancer Inst. 2014;107(1):378. https://doi.org/10.1093/jnci/dju378

Tan S, Pollack JR, Kaplan MJ, Colevas AD, West RB. BRAF inhibitor treatment of primary BRAF-mutant ameloblastoma with pathologic assessment of response. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122(1):e5-7. https://doi.org/10.1016/j.oooo.2015.12.016

Fernandes GS, Girardi DM, Bernardes JPG, Fonseca FP, Fregnani ER. Clinical benefit and radiological response with BRAF inhibitor in a patient with recurrent ameloblastoma harboring V600E mutation. BMC Cancer. 2018;18(1):887. https://doi.org/10.1186/s12885-018-4802-y

Hirschhorn A, Campino GA, Vered M, Greenberg G, Yacobi R, Yahalom R, et al. Upfront rational therapy in BRAF V600E mutated pediatric ameloblastoma promotes ad integrum mandibular regeneration. J Tissue Eng Regen Med. 2021;15(12):1155-61. https://doi.org/10.1002/term.3254

Pereira NB, Pereira KMA, Coura BP, Diniz MG, Castro WH, Gomes CC, et al. BRAFV600E mutation in the diagnosis of unicystic ameloblastoma. J Oral Pathol Med. 2016;45(10):780-5. https://doi.org/10.1111/jop.12443

Roskoski Jr R. Targeting oncogenic Raf protein-serine/threonine kinases in human cancers. Pharmacol Res. 2018;135:239-58. https://doi.org/10.1016/j.phrs.2018.08.013

Yakout NM, Abdallah DM, Abdelmonsif DA, Kholosy HM, Talaat IM, Elsakka O. BRAFV600E mutational status assessment in cutaneous melanocytic neoplasms in a group of the Egyptian population. Cancer Cell Int. 2023;23(1):17. https://doi.org/10.1186/s12935-023-02858-1

Chang JYF, Lu PH, Tseng CH, Wang YP, Lee JJ, Chiang CP. Factors affecting the accuracy of anti-BRAF V600E immunohistochemistry results in ameloblastomas. J Oral Pathol Med. 2023;52(4):342-50. https://doi.org/10.1111/jop.13399

Diagnostic accuracy of a mutation-specific monoclonal antibody (RM8 clone) for BRAF V600e detection by immunohistochemistry in ameloblastomas

Autores

DOI:

Palavras-chave:

Resumo

Referências

Downloads

Publicado

Como Citar

Edição

Seção

Licença

Enviar Submissão

Idioma

Volume 10 (2025)

Indexadores