EGFR expression is associated with increased cell turnover and poor histologic grade in human colon carcinomas

Abstract

21046 Background: The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase that is important for colon cancer cell growth and represents a therapeutic target. We studied EGFR expression in relation to rates of apoptosis and cell proliferation. Methods: TNM stage II and III colon carcinomas (n= 361) from patients treated in a 5-FU-based adjuvant trial were studied. EGFR expression (EGFR pharmDx™) and extent were analyzed and their relationship to rates of cell turnover, histologic grade, mismatch repair (MMR) status (defective if instability at BAT 26 locus plus loss of hMLH1, hMSH2 or hMSH6 proteins) and clinical outcome were determined. Results: EGFR plasma membrane staining was detected in 214 (59.3 %) colon carcinomas. Increased EGFR intensity (2+, 3+) was associated with a higher number of caspase-3- (p= 0.02) and Ki-67- (p< 0.001)positive tumor cells. Increased EGFR intensity (p= 0.02) and extent (p= 0.03) were associated with poor differentiation, and did not depend upon MMR status (Breslow-Day test p ≥ 0.46). Diffuse (vs. focal) EGFR extent was increased in tumors with defective MMR [22 of 32 (69%)] compared to those with intact MMR [136 of 271 (50%)] (p= 0.047). EGFR intensity was unrelated to MMR status. Neither EGFR intensity nor extent was significantly associated with patient survival. Conclusions: Stage II and III colon cancers with EGFR overexpression show adverse prognostic variables, i.e., increased rates of cell turnover and poor histologic grade, suggesting that EGFR may be an important target for adjuvant therapy. *Chi-square test for categorical data, Wilcoxin rank-sum test for continuous data [Table: see text] No significant financial relationships to disclose.