Differential expression and prognostic value of ERCC1 and thymidylate synthase in resected gastric adenocarcinoma.

Abstract

38 Background: Excision repair cross complementing gene-1 (ERCC1) and thymidylate synthase (TS) are key regulatory enzymes whose expression patterns are variably associated with overall survival (OS) in several malignancies. For example, in lung cancer, high ERCC1 expression is inversely associated with OS depending on whether or not patients receive perioperative chemotherapy with surgery. The expression pattern and prognostic value of ERCC1 and TS in resected gastric adenocarcinoma (GAC) are not known. Methods: 109 patients who underwent resection of GAC between 1/00-6/11 had tissue available for analysis. Primary objective was to assess for differential expression of ERCC1 and TS using immunohistochemistry. Secondary objective was to assess for association of ERCC1 and TS expression with OS. Results: Median age was 64yrs. Median FU was 21.2mos and median OS was 28.8mos. Resected GAC exhibited differential expression of ERCC1 (23% high, n=25) and TS (43% high, n=47). ERCC1 and TS expression were not associated with OS. In a planned subset analysis, however, of patients who received chemotherapy (n=73), high ERCC1 expression was associated with decreased OS (16.7 vs. 53.8mos; p=0.03). After controlling for tumor size, margin, grade, T-stage, lymph node involvement, and presence of lymphovascular or perineural invasion, the negative prognostic value of high ERCC1 expression persisted on multivariate Cox regression analysis (HR 2.5; 95%CI: 1.03-6.0; p=0.04). By contrast, in patients who underwent resection only (n=35), high ERCC1 expression was associated with improved OS (40.4 vs. 12.7mos; p=0.10). This finding persisted on multivariate analysis (HR 0.20; 95%CI: 0.04-.86; p=0.03). Conclusions: Resected gastric adenocarcinoma exhibits differential expression of TS and ERCC1. TS expression is not associated with OS. However, similar to what is reported in lung cancer, high ERCC1 tumor expression is associated with decreased OS in patients receiving chemotherapy, but is associated with increased OS in those treated with surgery alone. ERCC1 expression has prognostic value in resected gastric cancer and further investigation is warranted.