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Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours.
Cros, J; Sbidian, E; Hans, S; Roussel, H; Scotte, F; Tartour, E; Brasnu, D; Laurent-Puig, P; Bruneval, P; Blons, H; Badoual, C.
Afiliación
  • Cros J; Department of Pathology, G. Pompidou European Hospital APHP-Université Paris Descartes, Paris.
  • Sbidian E; Department of Public Health, University Paris Est Créteil-EA4393, Creteil.
  • Hans S; Departments of Head and Neck Surgery.
  • Roussel H; Department of Pathology, G. Pompidou European Hospital APHP-Université Paris Descartes, Paris.
  • Scotte F; Oncology, G. Pompidou European Hospital-Université Paris Descartes, Paris.
  • Tartour E; INSERM U970 Paris-Centre de recherche Cardiovasculaire Team 10, Paris.
  • Brasnu D; Departments of Head and Neck Surgery.
  • Laurent-Puig P; Department of Biochemistry and Molecular Oncology, G. Pompidou European Hospital-Université Paris Descartes, Inserm Unité Mixte de Recherche-S775, Paris, France.
  • Bruneval P; Department of Pathology, G. Pompidou European Hospital APHP-Université Paris Descartes, Paris.
  • Blons H; Department of Biochemistry and Molecular Oncology, G. Pompidou European Hospital-Université Paris Descartes, Inserm Unité Mixte de Recherche-S775, Paris, France.
  • Badoual C; Department of Pathology, G. Pompidou European Hospital APHP-Université Paris Descartes, Paris; INSERM U970 Paris-Centre de recherche Cardiovasculaire Team 10, Paris. Electronic address: cecile.badoual@egp.aphp.fr.
Ann Oncol ; 24(10): 2624-2629, 2013 Oct.
Article en En | MEDLINE | ID: mdl-23933559
BACKGROUND: Malignant tumours of the salivary glands (MSGT) are rare and pleomorphic entities. Patients with advanced disease may benefit from targeted therapy; however, specific targets for optimising and personalising treatments are yet to be identified. DESIGN: Immunohistochemistry for C-KIT, EGFR, HER2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was carried out and evaluated in terms of progression-free and overall survival. High throughput molecular screening of key oncogenes was done in 107 patients using routine diagnostic methods and Sequenom technology. RESULTS: Several therapy leads were identified, including high levels of HER2 and androgen receptors in salivary duct carcinomas, C-KIT in myoepithelial carcinomas and EGFR in mucoepidermoid carcinomas. Recurrent mutations involving downstream elements of the EGFR pathway were found in HRAS, notably in tumours with a myoepithelial component, and in other key oncogenes (KRAS/NRAS/PI3KCA/BRAF/MAP2K). On the other hand, <1% of samples had EGFR or HER2 mutations. CONCLUSION: Several tumour subtypes overexpressed targets of directed therapies suggesting potential therapy leads. Genotyping results suggest activation downstream of EGFR in 18 of the 107 samples that could be associated with low efficacy of EGFR inhibitors. Other molecules, such as PI3K/MEK or mTOR inhibitors, may have anti-tumour activity in this subgroup. The high mutation rate in HRAS highlights a novel key oncogenic event in MSGT.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de las Glándulas Salivales / Carcinoma Mucoepidermoide / Mioepitelioma Tipo de estudio: Prognostic_studies Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2013 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de las Glándulas Salivales / Carcinoma Mucoepidermoide / Mioepitelioma Tipo de estudio: Prognostic_studies Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2013 Tipo del documento: Article Pais de publicación: Reino Unido