Imaging, Diagnosis, Prognosis Tumor Epidermal Growth Factor Receptor and EGFRPY1068 Are Independent Prognostic Indicators for Head and Neck Squamous Cell Carcinoma

Purpose: To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC). Patients andMethods:HNSCC tumors frompatients prospectively enrolled in either an EarlyDetection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N 1⁄4 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N1⁄439)were evaluated for EGFR 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 (n1⁄467). Tumor (n1⁄450) EGFRandEGFRvIIImRNA levelswere quantified using real-time PCR. Results: EGFR expression by immunohistochemistry (IHC)was significantly higher in the EDRN tumors with EGFR gene amplification (P < 0.001), and a similar trendwas noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (P1⁄4 0.019 and P1⁄4 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 1⁄4 2.75; 95% confidence interval (CI) 1⁄4 1.26–6.00 and HR 1⁄4 3.29; 95% CI 1⁄4 1.34–8.14, respectively]. Conclusions: In two independentHNSCCcohorts treatedwith orwithout cetuximab, tumor EGFR levels were indicative of survival. Tumor EGFR PY1068 levels provided prognostic information independent of total EGFR. Clin Cancer Res; 18(8); 2278–89. 2012 AACR.