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

Abstract

Epidermal growth factor receptor (EGFR) is involved in the progression of many cancer types and represents an important therapeutic target. 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. 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. 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.