Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma

Sarah Wheeler, Doris R. Siwak, Raymond Chai, Courtney LaValle, Raja R. Seethala, Lin Wang, Kathleen Cieply, Carol Sherer, Corwin Joy, Gordon B. Mills, Athanassios Argiris, Jill M. Siegfried, Jennifer R. Grandis, Ann Marie Egloff

    Research output: Contribution to journalArticle

    60 Scopus citations

    Abstract

    Purpose: To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC). Patients and Methods: HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N = 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N = 39) 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 (n = 67). Tumor (n = 50) EGFR and EGFRvIII mRNA levels were 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 trend was noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (P =0.019 and P = 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]. Conclusions: 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.

    Original languageEnglish (US)
    Pages (from-to)2278-2289
    Number of pages12
    JournalClinical Cancer Research
    Volume18
    Issue number8
    DOIs
    StatePublished - Apr 15 2012

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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    Wheeler, S., Siwak, D. R., Chai, R., LaValle, C., Seethala, R. R., Wang, L., Cieply, K., Sherer, C., Joy, C., Mills, G. B., Argiris, A., Siegfried, J. M., Grandis, J. R., & Egloff, A. M. (2012). Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma. Clinical Cancer Research, 18(8), 2278-2289. https://doi.org/10.1158/1078-0432.CCR-11-1593