Epidermal growth factor receptor protein expression and genomic alterations in renal cell carcinoma

BACKGROUND: Epidermal growth factor receptor (EGFR) is involved in the progression of many cancer types and represents an important therapeutic target. METHODS: To determine the role of EGFR in renal cell carcinoma (RCC), the authors analyzed 1088 tumors in a tissue microarray format by using immunohistochemistry and fluorescence in situ hybridization (FISH). A subset of 63 cancers was sequenced for EGFR exon 18 through 21 mutations. RESULTS: EGFR expression was observed in 83.8% of clear cell carcinomas, in 68.2% of papillary carcinomas, in 75% of chromophobe carcinomas, and in 50% of oncocytomas. Within clear cell carcinomas, the expression level of EGFR was associated with high tumor grade (P<.0001), advanced pathologic tumor classification (P<.0001), and, to a lesser extent, lymph node status (P.0326). FISH analysis revealed increased EGFR copy numbers (high polysomy) in 5.5% of tumors and amplification in 0.1% of tumors. EGFR copy number increases were associated with EGFR protein expression (P.0015). Within clear cell carcinomas, EGFR copy number increases were associated with high tumor grade (P <.0001), advanced pathologic tumor classification (P.0472), and lymph node status (P.0065). No exon 18 through 21 mutations were identified in 63 sequenced tumors. CONCLUSIONS: The authors concluded that increased EGFR expression occurs in a fraction of patients who have RCC with an unfavorable histologic phenotype. EGFR copy number gain represents 1 possible cause for EGFR overexpression; however, many over expressing tumors have a normal genotype. High polysomy (which is suggested to be predictive of a response to tyrosine kinase inhibitors) occurs in 5.6% of RCCs. Thus, the potential utility of anti-EGFR medications may be worth further investigation in a small but significant subset of patients with RCC. Cancer 2012; 118: 1268-75. (C) 2011 American Cancer Society.