Potential role of ERBB-2 and cyclooxygenase-2 expression in human colon carcinomas

Abstract

3608 Background: ERBB2 receptor tyrosine kinase and cyclooxygenase-2 (COX-2) represent promising molecular targets for cancer therapy and/or prevention. This study investigates the relation between ERBB2 and COX-2 expression in human colon carcinomas. Methods: Immunohistochemistry to detect membranous ERBB2 and cytoplasmic COX-2 expression was performed on 124 archived human primary colon carcinomas and matched normal tissues. Results were expressed as % positive cells. In addition, the mRNA levels of ERBB2 and COX-2 were evaluated in a subset of the colonic tissue samples (46 tumor, 7 normal) using real time RT-PCR (expression relative to a calibrator) Results: The results are displayed in the table . ERBB2 and COX-2 expression was higher in well-differentiated tumors (p<0.001 and p<0.05, respectively). However, both ERBB2 and COX-2 protein levels increased in a statistically significant way towards more advanced stages. Linear regression revealed a strong positive correlation between ERBB2 and COX-2 expression in neoplastic populations (r=0.83, p=0.000082 for protein; r=0.411, p=0.00404 for mRNA). Thus, ERBB2 and COX-2 may transcriptionally regulate each other in colon carcinomas. Conclusions: Overexpression of ERBB2 and COX-2 may represent an early dysfunctional event in human colon carcinogenesis regarding tumor differentiation. However, their expression is increased in advanced stages. These markers may constitute important targets for chemoprevention or adjunct therapy of well-differentiated colon carcinomas. [Table: see text] No significant financial relationships to disclose.