Comparative Prognostic Value of Epidermal Growth Factor Quantitative Protein Expression Compared with FISH for Head and Neck Squamous Cell Carcinoma

Abstract

Purpose: Epidermal growth factor receptor (EGFR) overexpression correlates with recurrence and with treatment resistance in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to evaluate the relationship of EGFR gene copy number utilizing FISH and protein expression with automated quantitative analysis (AQUA) and to correlate those with patient outcome.Experimental Design: A tissue microarray composed of 102 HNSCC treated with (chemo)radiation was constructed and analyzed for EGFR copy number by FISH (Vysis; Abbott Laboratories) and EGFR protein expression using AQUA analysis of EGFR staining scored on a scale of 0 to 255. We evaluated associations of EGFR FISH status and AQUA score with clinicopathologic parameters and survival prognosis.Results: Eleven (17.2%) of 64 tumors with FISH results showed EGFR high polysomy and/or gene amplification (FISH positive). Protein levels assessed by AQUA in FISH-positive cases were significantly higher (P ¼ 0.04) than in FISH-negative cases. Using the continuous AQUA scores for EGFR expression, AQUA and FISH showed significant agreement (Pearson's r ¼ 0.353, P ¼ 0.04). Patients with high tumor EGFR protein expression had inferior 5-year overall survival (27.7%) compared with those with low tumor EGFR expression (54%; P ¼ 0.029). There was no significant association between EGFR FISH status and overall survival (P ¼ 0.201). In the multivariate model, high tumor EGFR protein expression status remained an independent prognostic factor for overall survival (P ¼ 0.047).Conclusions: EGFR protein content correlates with gene copy number if protein content is quantitated and automatically analyzed, as with AQUA. EGFR protein levels assessed by AQUA strongly predict for patient outcome in HNSCC, whereas EGFR FISH status does not provide prognostic information. Clin Cancer Res; 17(9); 2947-54. Ó2011 AACR.

Epidermal Growth Factor Receptor Protein Detection in Head and Neck Cancer Patients: A Many-Faceted Picture

“…Tumoral EGFR protein expression has been widely investigated in HNSCC patients, with different measurement methods and variable prognostic cutoff values (2,3,11,15,25). Here we present a comparison between IHC, WB, and binding assays for the measurement of tumor EGFR expression in a homogenous prospective series of 79 high-risk head and neck cancer patients.…”

“…Furthermore, compared with a full analysis of paraffin blocks, histospots on TMA might not be entirely "representative" of the entire tumor. Thus, visual assessment by a pathologist may target tumor cell staining in an operator-dependent way (11). Although this may be an advantage for tumor cell EGFR detection, there is no uniform scoring system (12), and the interpretation of staining intensity remains somewhat subjective (9).…”

“…Among them, immunohistochemical staining of EGFR in paraffin-embedded tumor tissue is the most widely employed [e.g., in the Radiation Therapy Oncology Group (RTOG) 9003 study; refs. 3,11], for either visual (12) or automated EGFR determination (11). 125 I-EGF radioreceptor assays have also been used to quantify high-affinity EGF-binding sites in membrane preparations from human tumors (13).…”

CT Imaging Correlates of Genomic Expression for Oral Cavity Squamous Cell Carcinoma

“…Increased EGFR has correlated previously with worse stage and prognosis with treatment resistance. 18,19,26 The association between size with mass effect and invasion, which also correlated with EGFR expression, may help to elucidate the association with tumor grade. The grouping of clinical and imaging findings into representative phenotypes could not only help in understanding and predicting genomic expression but also reinforce imagers' search patterns and the risk for invasion, which may not be directly visualized on imaging.…”

“…Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor on the cell surface related to cell growth that is both a predictive biomarker in head and neck squamous cell carcinoma 18,19 and a chemotherapy target. 3,20 EGFR expression has been related to the ratio of contrast-enhanced tumor and necrosis in brain tumors 9 and primary tumor size and nodal metastasis for breast cancer.…”