Prognostic Value of ERCC1, Thymidylate Synthase, and Glutathione S-Transferase &pgr; for 5-FU/Oxaliplatin Chemotherapy in Advanced Colorectal Cancer

Background:The aim of this study was to determine whether the expression of the excision repair cross-complementing 1 (ERCC1), thymidylate synthase (TS) and glutathione S-transferase &pgr; (GST&pgr;) predict clinical outcome in patients with advanced colorectal cancer treated with fluorouracil (5-FU)/oxaliplatin chemotherapy. Methods:The study population consisted of 70 patients with advanced colorectal cancer (median age, 54 years). Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion on days 1 plus leucovorin (LV) 20 mg/m2 over 10 minutes, followed by 5-FU bolus 400 mg/m2 and a 22-hour continuous infusion of 600 mg/m2 from day 1 to 2. Treatment was repeated at 2-week intervals. The expression of ERCC1, TS, and GST&pgr; in primary tumors was examined using immunohistochemistry. Results:ERCC1, TS, and GST&pgr; were positive in 55.7%, 68.6%, and 71.4% of cases, respectively. Patients without TS expression were more likely to respond to chemotherapy (P = 0.009). There were no significant differences between response to treatment and the ERCC1 or GST&pgr; expression pattern (P = 0.768, P = 0.589, respectively). The median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0474). Patients who were ERCC1 positive combined with TS positive, or those with ERCC1 positive combined with TS positive and GST&pgr; positive had a poor OS (P = 0.0017, P = 0.0323, respectively). Multivariate analysis revealed that both ERCC1 and TS expression significantly impacted OS (hazard ratio 1.72, P = 0.023). Conclusion:Immunohistochemical study of ERCC1 and TS may be useful for the prediction of clinical outcome in patients with advanced colorectal cancer treated with 5-FU and oxaliplatin.