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EGFR status and KRAS/BRAF mutations in intestinal-type sinonasal adenocarcinomas

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Abstract

Background

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumour that is etiologically related to professional exposure to wood dust and exhibits a poor prognosis. Treatment alternatives to surgery and radiotherapy are needed and may be found in anti-EGFR agents. EGFR gene copy number gains and KRAS/BRAF mutations have been reported to act as positive and negative predictors, respectively, of therapeutic response to EGFR targeted therapies in colorectal adenocarcinoma, a tumour type claimed to be genetically similar to ITAC. Therefore, the aim of this study was to evaluate the occurrence and consequence of EGFR alterations and KRAS and BRAF mutations in a large series of ITAC.

Methods

EGFR protein expression was studied in 98 paraffin embedded tissue samples, organized in a tissue microarray. Gene copy number analysis was performed by FISH using the same tissue microarray, complemented by microarray CGH and MLPA analysis on DNA extracted from 65 fresh frozen tissues. Mutations in EGFR, KRAS and BRAF were analysed by direct sequencing on 65 fresh frozen tissues.

Results

EGFR gene copy number gains were observed in 45 %, and protein over-expression in 21 % of the cases. No mutations were found in EGFR or BRAF, while KRAS mutations were present in 12 % of the cases. Neither protein overexpression nor gene copy number gain correlated to histological subtype, tumour stage or clinical follow-up.

Conclusion

In the largest series of ITAC published to date, and using a number of different techniques, EGFR alterations were frequently observed. Although apparently not useful as a prognostic factor, there may be a basis for investigating EGFR targeted therapies in this group of patients, especially because negative response predictors such as KRAS and BRAF mutations are infrequent or absent, respectively.

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Acknowledgments

This study was supported by grant PI05-1387, PI08-1599 and EMER07-048 of Fondos de Investigación Sanitaria (FIS) and RD06/0020/0034 of Red Temática de Investigación Cooperativa en Cáncer (RTICC), Spain, and the FEDER Funding Program from the European Union. The authors thank Sira Potes and Eva Allonca for the tissue microarray preparation and the immunohistochemical experiments.

Author information

Authors and Affiliations

  1. Department of Otolaryngology, IUOPA, Hospital Universitario Central de Asturias, Oviedo, Spain

    Cristina García-Inclán, Fernando López, Jhudit Pérez-Escuredo, Mari Paz Cuesta-Albalad, Carlos Suárez, José Luis Llorente & Mario A. Hermsen

  2. Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain

    Blanca Vivanco

  3. Department of Molecular Oncology, IUOPA, Hospital Universitario Central de Asturias, Oviedo, Spain

    Irene Centeno & Milagros Balbín

  4. Departamento de Otorrinolaringología, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Hospital Universitario Central de Asturias, Edificio H Covadonga 1ª Planta Centro, lab 2, Celestino Villamil s/n, 33006, Oviedo, Spain

    Mario A. Hermsen

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  1. Cristina García-Inclán
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Correspondence to Mario A. Hermsen.

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García-Inclán, C., López, F., Pérez-Escuredo, J. et al. EGFR status and KRAS/BRAF mutations in intestinal-type sinonasal adenocarcinomas. Cell Oncol. 35, 443–450 (2012). https://doi.org/10.1007/s13402-012-0103-7

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  • DOI: https://doi.org/10.1007/s13402-012-0103-7

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