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01-12-2024 | Ameloblastoma | Research

BRAF p.V600E Mutational Status Does Not Correlate with Biological Behavior in Conventional Ameloblastomas: A Disease-Free Survival Analysis

Authors: Allan Vinícius Martins-de-Barros, Fábio Andrey da Costa Araújo, Tatiane Fonseca Faro, Arthur Alves Thomaz de Aquino, Adauto Gomes Barbosa Neto, Helker Albuquerque Macedo da Silva, Elker Lene Santos de Lima, Maria Tereza Cartaxo Muniz, Emanuel Dias de Oliveira e Silva, Marianne de Vasconcelos Carvalho

Published in: Head and Neck Pathology | Issue 1/2024

Abstract

Background

Dysregulation of the MAPK pathway appears to exert a pivotal role in the pathogenesis of ameloblastomas, since BRAF p.V600E has been reported in over 65% of the tumors. Therefore, the purpose of this study was to investigate whether the BRAF p.V600E is related to biological behavior and disease-free survival in patients with conventional ameloblastomas.

Methods

This is a retrospective cohort study based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations. The study population consisted of individuals treated for conventional ameloblastomas. Clinical, imaging, histomorphological, immunohistochemical (Ki67 and CD138/syndecan-1), and molecular BRAF p.V600E mutation analyses were performed. Bivariate statistical analysis was performed through chi-square and Fisher’s exact tests. Kaplan–Meier analysis with log-rank test and Cox proportional hazards regression were used to identify predictors of disease-free survival, with a significance level of 5%.

Results

Forty-one individuals were included, with a male-to-female ratio of 1.15:1. BRAF p.V600E mutation was identified in 75.6% of the tumors. No association between the BRAF mutational status and other clinical, imaging, histomorphological, and immunohistochemical variables was observed. Only the initial treatment modality was significantly associated with a better prognosis in univariate (p = 0.008) and multivariate (p = 0.030) analyses, with a hazard ratio of 9.60 (95%IC = 1.24–73.89), favoring radical treatment.

Conclusion

BRAF p.V600E mutation emerges as a prevalent molecular aberration in ameloblastomas. Nevertheless, it does not seem to significantly affect the tumor proliferative activity, CD138/syndecan-1-mediated cell adhesion, or disease-free survival outcomes.

WHO Classification of Tumours Editorial Board (2022) Head and neck tumours. Lyon (France): International Agency for Research on Cancer. https://publications.iarc.fr/. Accessed 20 Dec 2023

Effiom OA, Ogundana OM, Akinshipo AO, Akintoye SO (2018) Ameloblastoma: current etiopathological concepts and management. Oral Dis 24(3):307–316. https://doi.org/10.1111/odi.12646CrossRefPubMed

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(7):1649–1661. https://doi.org/10.1007/s00405-015-3631-8CrossRefPubMed

Martins-de-Barros AV, Silva CCG, Gonçalves KKN, Almeida RAC, Silva EDO, Araújo FAC, Robinson L, van Heerden WFP, Carvalho MV (2023) Does BRAF V600E mutation affect recurrence rate of ameloblastomas? Systematic review and meta-analysis. J Oral Pathol Med 52(8):701–709. https://doi.org/10.1111/jop.13458CrossRefPubMed

Kurppa KJ, Catón J, Morganv PR, Ristimäki A, Ruhin B, Kellokoski J, Elenius K, Heikinheimo K (2014) High frequency of BRAF V600E mutations in ameloblastoma. J Pathol 232(5):492–498. https://doi.org/10.1002/path.4317CrossRefPubMedPubMedCentral

Cantwell-Dorris ER, O’Leary JJ, Sheils OM (2011) BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther 10(3):385–394. https://doi.org/10.1158/1535-7163.MCT-10-0799CrossRefPubMed

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, Initiative STROBE (2008) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61(4):344–349CrossRef

Fulawka L, Halon A (2016) Proliferation index evaluation in breast cancer using ImageJ and ImmunoRatio applications. Anticancer Res 36(8):3965–3972PubMed

Nadalin MR, Fregnani ER, Silva-Sousa YTC, Perez DEC (2011) Syndecan-1 (CD138) and Ki-67 expression in odontogenic cystic lesions. Braz Dent J 22(3):223–229. https://doi.org/10.1590/s0103-64402011000300008CrossRefPubMed

10.

Fregnani ER, Perez DEC, Almeida OP, Fonseca FP, Soares FA, Castro-Junior G, Alves FA (2017) BRAF-V600E expression correlates with ameloblastoma aggressiveness. Histopathology 70(3):473–484. https://doi.org/10.1111/his.13095CrossRefPubMed

11.

Yang YC, Wang JJ, Huang Y, Cai WX, Tao Q (2021) Development and validation of a prognostic nomogram for postoperative recurrence-free survival of ameloblastoma. Cancer Manag Res 13:4403–4416. https://doi.org/10.2147/CMAR.S307517CrossRefPubMedPubMedCentral

12.

Heikinheimo K, Kurppa KJ, Elenius K (2015) Novel targets for the treatment of ameloblastoma. J Dent Res 94(2):237–240. https://doi.org/10.1177/0022034514560373CrossRefPubMedPubMedCentral

13.

Brown NA, Rolland D, McHugh JB, Weigelin HC, Zhao L, Lim MS, Elenitoba-Johnson KSJ, Betz BL (2014) Activating FGFR2-RAS-BRAF mutations in ameloblastoma. Clin Cancer Res 20(21):5517–5526. https://doi.org/10.1158/1078-0432.CCR-14-1069CrossRefPubMed

14.

Martins-de-Barros AV, Anjos RS, Silva CCG, Silva EDO, Araújo FAC, Carvalho MV (2022) 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 51(3):223–230. https://doi.org/10.1111/jop.13278CrossRefPubMed

15.

Fuji S, Ishibashi T, Kokura M, Fujimoto T, Matsumoto S, Shidara S, Kurppa JK, Pape J, Caton J, Morgan PR, Heikinheimo K, Kikuchi A, Jimi E, Kiyoshima T (2022) RAF1-MEK/ERK pathway-dependent ARL4C expression promotes ameloblastoma cell proliferation and osteoclast formation. J Pathol 256(1):119–133. https://doi.org/10.1002/path.5814CrossRef

16.

Kondo S, Ota A, Ono T, Karnan S, Wahiduzzaman M, Hyodo T, Rahman ML, Ito K, Furuhashi A, Hayashi T, Konishi H, Tsuzuki S, Hosokawa Y, Kazaoka Y (2020) Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma. Cancer Med 9(8):2904–2917. https://doi.org/10.1002/cam4.2931CrossRefPubMedPubMedCentral

17.

Oh KY, Cho SD, Yoon HJ, Lee JI, Ahn SH, Hong SD (2019) High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: clinicopathological significance and correlation with epithelial-mesenchymal transition. J Oral Pathol Med 48(5):413–420. https://doi.org/10.1111/jop.12851CrossRefPubMed

18.

Diniz MG, Guimarães BVA, Pereira NB, Menezes GHF, Gomes CC, Gomez RS (2017) DNA damage response activation and cell cycle dysregulation in infiltrative ameloblastomas: a proposed model for ameloblastoma tumor evolution. Exp Mol Pathol 102(3):391–395. https://doi.org/10.1016/j.yexmp.2017.04.003CrossRefPubMed

19.

Jabbarzadeh M, Hamblin MR, Pournaghi-Azar F, Saatloo MV, Kouhsoltani M, Vahed N (2021) Ki-67 expression as a diagnostic biomarker in odontogenic cysts and tumors: a systematic review and meta-analysis. J Dent Res Dent Clin Dent Prospects 15(1):66–75. https://doi.org/10.34172/joddd.2021.012CrossRefPubMedPubMedCentral

20.

Whitfield ML, George LK, Grant GD, Perou CM (2006) Common markers of proliferation. Nat Rev Cancer 6(2):99–106. https://doi.org/10.1038/nrc1802CrossRefPubMed

21.

Minh TBD, Duc TN, Thanh VPN, Le TD, Tong MD, Nguyen TH, Tuan AL, Nguyen KX, Viet TT, Ta TB, Nguyen ST, Vu HA, Nguyen BV, Ngoc DNT, Quoc VT, Duc TB (2023) Relationships of BRAF V600E gene mutation with some immunohistochemical markers and recurrence rate in patients with thyroid carcinoma. Clin Med Insights Oncol 28(17):11795549231203504. https://doi.org/10.1177/11795549231203503CrossRef

22.

Chen J, Zhang G, Liu X, Tu P (2023) The association of BRAF V600E gene mutation with proliferative activity and histopathological characteristics of congenital melanocytic nevi in children. An Bras Dermatol 98(4):498–505. https://doi.org/10.1016/j.abd.2022.01.016,2023CrossRefPubMedPubMedCentral

23.

Etemad-Moghadam S, Alaeddini M (2017) A comparative study of syndecan-1 expression in different odontogenic tumors. J Oral Biol Craniofac Res 7(1):23–26. https://doi.org/10.1016/j.jobcr.2016.11.001CrossRefPubMed

24.

Carreón-Burciaga RG, González-González R, Molina-Frechero N, López-Verdín S, Pereira-Prado V, Bologna-Molina R (2018) Differences in E-cadherin and syndecan-1 expression in different types of ameloblastomas. Anal Cell Pathol (Amst) 2018:9392632. https://doi.org/10.1155/2018/9392632CrossRefPubMed

25.

Bologna-Molina R, Mosqueda-Taylor A, Lopez-Corella E, Almeida OP, Carrasco-Daza D, Garcia-Vazquez F, Farfan-Morales JE, Irigoyen-Camacho ME, Damián-Matsumura P (2008) Syndecan-1 (CD138) and Ki-67 expression in different subtypes of ameloblastomas. Oral Oncol 44(8):805–811. https://doi.org/10.1016/j.oraloncology.2007.10.007CrossRefPubMed

26.

Menon S, Kumar V, Archana S, Nath P, Shivakotee S, Hoda M (2019) Ameloblastoma management: “horses for courses” protocol. J Maxillofac Oral Surg 18(3):400–404. https://doi.org/10.1007/s12663-019-01189-xCrossRefPubMedPubMedCentral

27.

Hresko A, Burtyn O, Pavlovskiy L, Snisarevskyi P, Lapshyna J, Chepurnyi Y, Kopchak A, Karagozoglu KH, Forouzanfar T (2021) Controversies in ameloblastoma management: evaluation of decision making, based on a retrospective analysis. Med Oral Patol Oral Cir Bucal 26(2):e181–e186. https://doi.org/10.4317/medoral.24104CrossRefPubMed

28.

Bonacina R, Indi A, Massazza G, Rulli E, Gianatti A, Mandalà M, Ameloblastoma Cooperative Group (2022) Correlation of BRAF mutational status with clinical characteristics and survival outcomes of patients with ameloblastoma: the experience of 11 Italian centres. J Clin Pathol 75(8):555–559. https://doi.org/10.1136/jclinpath-2021-207527CrossRef

Title: BRAF p.V600E Mutational Status Does Not Correlate with Biological Behavior in Conventional Ameloblastomas: A Disease-Free Survival Analysis
Authors: Allan Vinícius Martins-de-Barros
Fábio Andrey da Costa Araújo
Tatiane Fonseca Faro
Arthur Alves Thomaz de Aquino
Adauto Gomes Barbosa Neto
Helker Albuquerque Macedo da Silva
Elker Lene Santos de Lima
Maria Tereza Cartaxo Muniz
Emanuel Dias de Oliveira e Silva
Marianne de Vasconcelos Carvalho
Publication date: 01-12-2024
Publisher: Springer US
Keywords: Ameloblastoma
Ameloblastoma
Published in: Head and Neck Pathology / Issue 1/2024
Electronic ISSN: 1936-0568
DOI: https://doi.org/10.1007/s12105-024-01621-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

BRAF p.V600E Mutational Status Does Not Correlate with Biological Behavior in Conventional Ameloblastomas: A Disease-Free Survival Analysis

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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