Oncotarget

Research Papers:

Epidermal growth factor receptor variant III in head and neck squamous cell carcinoma is not relevant for targeted therapy and irradiation

Dominik Thomas Koch, Anja Pickhard, Lena Gebel, Anna Maria S. Buchberger, Murat Bas, Carolin Mogler, Rudolf Reiter, Guido Piontek and Markus Wirth _

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Oncotarget. 2017; 8:32668-32682. https://doi.org/10.18632/oncotarget.15949

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Abstract

Dominik Thomas Koch1, Anja Pickhard1, Lena Gebel1, Anna Maria S. Buchberger1, Murat Bas1, Carolin Mogler2, Rudolf Reiter3, Guido Piontek1, Markus Wirth1

1Department of Otorhinolaryngology Head and Neck Surgery, Technical University of Munich, 81675 Munich, Germany

2Institute of Pathology, Technical University of Munich, 81675 Munich, Germany

3Department of Otolaryngology Head and Neck Surgery, Section of Phoniatrics and Pedaudiology, University of Ulm, 89070 Ulm, Germany

Correspondence to:

Markus Wirth, email: markus.wirth@tum.de

Keywords: head and neck squamous cell cancer, EGFR variant III, cetuximab, TKI, radiation

Received: October 11, 2016     Accepted: February 21, 2017     Published: March 06, 2017

ABSTRACT

Background: The epidermal growth factor receptor (EGFR) is an important regulator of cell growth and survival, and is highly variable in tumor cells. The most prevalent variation of the EGFR extracellular domain is the EGFR variant III (EGFRvIII). Some studies imply that EGFRvIII may be responsible for the poor response to the monoclonal EGFR-antibody Cetuximab, used therapeutically in head and neck squamous cell carcinoma (HNSCC). Due to inconsistent data in the literature regarding EGFRvIII prevalence and clinical relevance in HNSCC, especially its predictive value, we examined EGFRvIII-transfected cell lines and patient tissue samples.

Results: In contrast to other recent publications, we were able to demonstrate EGFRvIII expression in HNSCC. However, we noted that the different detection methods yielded inconsistent results. Furthermore, our EGFRvIII transfected and EGFR wild type cell lines exhibited similar characteristics and response rates in the performed in vitro experiments.

Materials and Methods: We conducted various inhibition and combined irradiation experiments using three EGFRvIII-transfected cell lines. Moreover, a patient cohort of 149 cases consisting of formalin fixed and paraffin embedded (FFPE) and fresh-frozen specimens was assayed via reverse transcriptase PCR (rtPCR) with gel electrophoresis and sequencing for EGFRvIII prevalence. In the rtPCR assays, we used five previously published EGFRvIII primers and EGFRvIII-positive glioblastoma tissue as a positive control. In addition, immunohistochemical staining was conducted.

Conclusions: EGFRvIII can be detected in HNSCC patient samples. Nevertheless, the low prevalence and similar response rates to targeted drugs and irradiation in vitro cast doubt regarding the clinical relevance of EGFRvIII in HNSCC.


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