Abstract
BackgroundWe examine the potential prognostic and predictive roles of EGFR variant III mutation, EGFR gene copy number (GCN), human papillomavirus (HPV) infection, c-MET and p16INK4A protein expression in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).MethodsWe analyzed the archival tumor specimens of 53 patients who were treated in 4 phase II trials for R/M SCCHN. Two trials involved the EGFR inhibitor erlotinib, and 2 trials involved non-EGFR targeted agents. EGFRvIII mutation was determined by quantitative RT-PCR, HPV DNA by Linear Array Genotyping, p16 and c-MET protein expression by immunohistochemistry, and EGFR GCN by FISH.ResultsEGFRvIII mutation, detected in 22 patients (42%), was associated with better disease control, but no difference was seen between erlotinib-treated versus non-erlotinib treated patients. EGFRvIII was not associated with TTP or OS. The presence of HPV DNA (38%), p16 immunostaining (32%), c-MET high expression (58%) and EGFR amplification (27%), were not associated with response, TTP or OS.ConclusionEGFRvIII mutation, present in about 40% of SCCHN, appears to be an unexpected prognostic biomarker associated with better disease control in R/M SCCHN regardless of treatment with erlotinib. Larger prospective studies are required to validate its significance.
Highlights
We examine the potential prognostic and predictive roles of epidermal growth factor receptor (EGFR) variant III mutation, EGFR gene copy number (GCN), human papillomavirus (HPV) infection, c-MET and p16INK4A protein expression in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)
EGFRvIII is proposed to account for limitations in response to current EGFR inhibitors, in patients with SCCHN tumors harboring EGFRvIII response to EGFR tyrosine kinase inhibition (TKI) is unknown
We examine the prevalence of EGFRvIII, HPV, p16, c-MET and EGFR GCN in patients with R/M SCCHN and explore the potential prognostic and predictive roles of these biomarkers in patients treated with or without EGFR TKI
Summary
We examine the potential prognostic and predictive roles of EGFR variant III mutation, EGFR gene copy number (GCN), human papillomavirus (HPV) infection, c-MET and p16INK4A protein expression in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of squamous cell carcinoma of the head and neck (SCCHN) and has been postulated to be a key molecular target in this malignancy [1]. The most common EGFR truncation mutation, EGFR variant III (EGFRvIII), harbors an in-frame deletion of exons 2 to 7 (801 bp), resulting in a truncated extracellular EGF-binding domain that is constitutively activated and ineffectively ubiquinated [11,12]. EGFRvIII is proposed to account for limitations in response to current EGFR inhibitors, in patients with SCCHN tumors harboring EGFRvIII response to EGFR tyrosine kinase inhibition (TKI) is unknown
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