Data from Tumor Epidermal Growth Factor Receptor and EGFR PY1068 Are Independent Prognostic Indicators for Head and Neck Squamous Cell Carcinoma

Abstract

<div>Abstract<p><b>Purpose:</b> To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC).</p><p><b>Patients and Methods:</b> HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (<i>N</i> = 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (<i>N</i> = 39) were evaluated for <i>EGFR</i> gene amplification by FISH and EGFR protein by immunohistochemical staining. Fresh-frozen tumors (EDRN) were also evaluated for EGFR protein and site-specific phosphorylation at Y992 and Y1068 using reverse-phase protein array (<i>n</i> = 67). Tumor (<i>n</i> = 50) EGFR and EGFRvIII mRNA levels were quantified using real-time PCR.</p><p><b>Results:</b> EGFR expression by immunohistochemistry (IHC) was significantly higher in the EDRN tumors with <i>EGFR</i> gene amplification (<i>P</i> < 0.001), and a similar trend was noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (<i>P</i> = 0.019 and <i>P</i> = 0.06, respectively). Elevated expression of total EGFR and EGFR PY1068 were independently significantly associated with reduced progression-free survival in the EDRN cohort [HR = 2.75; 95% confidence interval (CI) = 1.26–6.00 and HR = 3.29; 95% CI = 1.34–8.14, respectively].</p><p><b>Conclusions:</b> In two independent HNSCC cohorts treated with or without cetuximab, tumor EGFR levels were indicative of survival. Tumor EGFR PY1068 levels provided prognostic information independent of total EGFR. <i>Clin Cancer Res; 18(8); 2278–89. ©2012 AACR</i>.</p></div>