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Correlation of BRAF mutational status with clinical characteristics and survival outcomes of patients with ameloblastoma: the experience of 11 Italian centres
  1. Riccardo Bonacina1,
  2. Alice Indini2,
  3. Gabriella Massazza3,
  4. Eliana Rulli4,
  5. Andrea Gianatti3,
  6. Mario Mandalà5,6
  7. Ameloblastoma Cooperative Group
    1. 1Department of Dentistry, ASST Papa Giovanni XXIII, Bergamo, Italy
    2. 2Medical Oncology Unit, Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
    3. 3Pathology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
    4. 4Methodology for Clinical Research Laboratory, Oncology Department, Mario Negri Institute for Pharmacological Research, Milano, Italy
    5. 5Unit of Medical Oncology, Department of Oncology and Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy
    6. 6Medical Oncology, University of Perugia School of Medicine and Surgery, Perugia, Italy
    1. Correspondence to Professor Mario Mandalà, University of Perugia School of Medicine and Surgery, Perugia 06126, Italy; mario.mandala{at}unipg.it

    Abstract

    Aims Ameloblastoma is a rare odontogenic tumour with an aggressive local behaviour. Mutations in the mitogen-activated protein kinase pathway, namely BRAF V600E mutations, are a common finding. To date, there is no clear correlation between BRAF V600 mutation and clinical outcome.

    Methods We retrospectively reviewed the medical records of patients who underwent surgery for ameloblastoma between May 1998 and June 2018, at 11 participating Italian centres. BRAF mutational status was evaluated by quantitative PCR/pyrosequencing. The primary end points were to determine BRAF mutational status in primitive and recurrent ameloblastoma, and to assess the relapse-free interval (RFI); the secondary end point was to investigate the correlation of BRAF mutational status with the clinical features of the tumour and survival outcomes.

    Results Overall, 74 patients were included: 33 (44.5%) were BRAF wild type and 41 (55.4%) BRAF V600 mutated. BRAF V600 mutated ameloblastomas occurred more frequently in younger patients (p=0.0031), were located at the mandible (p=0.0009) and presented with unicystic variant. After a median follow-up of 60 months, 21 (28.3%) patients relapsed (30.3% and 26.8% in the BRAF wild type and BRAF mutated group, respectively). At univariable Cox models, none of the investigated variables, including microscopic margin involvement, was associated with RFI.

    Conclusions Local recurrence occurs in 30% of patients with ameloblastoma. BRAFV600 mutation is associated with younger age, mandibular localisation and with unicystic ameloblastoma. Neither BRAF mutation nor microscopically positive surgical margins were associated with RFI. Further studies are needed to elucidate outcomes of this rare disease according to clinical, histopathological and comprehensive molecular features.

    • bone neoplasms
    • neoplasms
    • oncogenes

    Data availability statement

    Data are available on reasonable request.

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    Data availability statement

    Data are available on reasonable request.

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    Footnotes

    • RB and AI are joint first authors.

    • AG and MM are joint senior authors.

    • Handling editor Runjan Chetty.

    • RB and AI contributed equally.

    • Collaborators We thank all the members of the Ameloblastoma Cooperative Group for their significant contribution to this work: Camilla Lucca, Laura Moneghini, Alessandro Remigio Bolzoni, Carlo Della Rocca, Giordana Bettini, Giorgia Saia, Stella Vanna Muria, Umberto Mariani, Alessandro Bardazzi, Francesco Erdini, Giovanni Lodi, Aldo Bruno Giannì, Luca Francetti, Alberto Bedogni, Giuseppe Spinelli, Umberto Romeo, Valentino Valentini, Antonella Polimeni, Carlo Della Rocca, Monica Pentenero, Adriano Piattelli, Andrea Cassoni, Matteo Nicolotti, Roberto Pistilli, Massimo Robiony, Antonino Cassisi, Luca Calabrese, and Daniela Massi.

    • Contributors RB: contributed to conception, design, data acquisition and interpretation, initial draft and final revision of the manuscript. AI: contributed to conception, design, data acquisition and interpretation, initial draft and final revision of the manuscript. GM: contributed to data acquisition, and final revision of the manuscript. ER: contributed to data acquisition and interpretation, initial draft and final revision of the manuscript. AG: contributed to conception, design, supervision and critically revised the manuscript. MM: contributed to conception, design, supervision and critically revised the manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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