Abstract 3739: Clinicopathologic significance of ERCC1, Thymidylate Synthase and Glutathione S-Transferase P1 expression for advanced gastric cancer patients receiving adjuvant 5-FU and cisplatin chemotherapy

Abstract

Abstract Background: The aim of this study was to determine whether expressions of the excision cross-complementing (ERCC1), thymidylate synthase (TS) and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric cancer treated with adjuvant 5-fluorouracil (5-FU) and cisplatin (FP) chemotherapy. Patients and methods: The study population consisted of 149 advanced gastric cancer patients. After curative resection, if the patients had stage II or higher disease, we administered adjuvant FP combination chemotherapy. The FP regimen was as follows. Cisplatin 60 mg/m2 was administered intravenously on day 1, and 5-FU 1,000 mg/m2 was administered intravenously on days 1 to 5. This regimen was repeated every three weeks. The expressions of ERCC1, TS and GSTP1 of primary tumors were examined by immunohistochemistry. Clinicopathologic information, including tumor size, histological grade, Lauren's classification, Borrmann type, vascular invasion, ratio of involved lymph nodes to dissected nodes, stage, carcinoembryonic antigen (CEA), and disease-free survival (DFS) and overall survival (OS) were evaluated with respect to the expressions of ERCC1, TS and GSTP1. Results: Median follow-up duration was 65.2 months, and median patient age was 51 ± 11 years (range 24-75). The positive rates of ERCC1, TS, and GSTP1 were 63.1%, 76.5%, and 40.3%, respectively. ERCC1 and GSTP1 expression was significantly correlated with size (p = 0.040, p = 0.018, respectively). Positive relationships were found between the expression of TS and Borrmann type (p = 0.030) and stage (p = 0.041). Univariate analysis showed that Lauren classification, stage, positive lymph node ratio, and type of operation were associated with both DFS and OS. ERCC1 and GTP1 were significant variables affecting OS (p = 0.005, p = 0.024, respectively). Patients who were both ERCC1 and GSTP1 positive had longer survival (p = 0.003). Multivariate analysis revealed that stage and positive lymph node ratio were independently associated with DFS and OS. Expression of both ERCC1 and GSTP1significantly impacted on OS (hazard ratio = 0.069, p = 0.021). Conclusion: Immunohistochemical studies for ERCC1 and GSTP1 were useful in prediction of the clinical outcome in advanced gastric cancer patients treated with adjuvant FP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3739.