Significance of ERCC1 and HER2 expression in human colon carcinomas

Abstract

14534 Background: Predictive and prognostic markers need to be established in colon cancer in order to tailor chemotherapy and, therefore, improve efficacy of adjuvant treatment. In this study, expression of the excision repair cross-complementing 1 (ERCC1) and HER2 tyrosine kinase receptor genes was evaluated in human colon carcinomas. Moreover, expression levels were associated with survival, time to disease progression and various clinicopathologic parameters. Methods: Fifty formalin fixed paraffin embedded tissues of primary colon carcinomas, resected from an equal number of patients at the University Hospital of Patras, Greece were studied. Forty four patients were treated with adjuvant chemotherapy and four patients with chemotherapy for advanced disease. Total RNA was extracted from tissues, quantified and reverse transcribed. Levels of ERCC1 and HER2 mRNA were quantified using Taqman probes in real time PCR and expressed relative to a calibrator. Results: ERCC1 and HER2 mRNA were detected in 92% and 82% of cases respectively, although overexpression was observed in 43.5% and 26.8%. Levels of expression were not related to age, stage, grade and overall survival. There was a significant association between overexpression of ERCC1 and time to disease progression (p<0.05) although this was not observed for HER2. There was a trend towards decreased relapse following adjuvant therapy in patients with low expression levels of ERCC1 and HER2 mRNA levels. However this difference failed to reach significance. Expression levels of ERCC1 and HER2 were not correlated with each other. Furthermore, coexpression of the two molecules was not related to time to disease progression. Additionally, 99.5% and 93.7% of patients with low expression of ERCC1 and HER2, respectively, having received adjuvant therapy were alive at the 36 months follow up. Conclusions: These data suggest that overexpression of ERCC1 is significantly associated with time to disease progression in colon cancer. Further studies of ERCC1 as a prognostic or predictive marker are warranted. No significant financial relationships to disclose.