Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatin

Abstract

Increased expression of thymidylate synthase (TS) is thought to be associated with resistance to antifolate drugs such as pemetrexed. Excision repair cross-complementation group 1 (ERCC1) is a predictive marker for platinum-based chemotherapy. This study evaluated whether the expression of TS and ERCC1 proteins is associated with clinical outcomes of the patients with pulmonary adenocarcinoma who were treated with pemetrexed/cisplatin as first-line chemotherapy. The expressions of TS and ERCC1 were evaluated by immunohistochemistry in biopsy specimens obtained from patients with pulmonary adenocarcinoma who had received pemetrexed/cisplatin as first-line treatment. Patients were categorized according to median H-score. Response rate (RR), progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively. Both low TS and ERCC1 expressions were significantly associated with better RR (p = 0.037 and p = 0.015, respectively) and longer PFS (p < 0.001 and p = 0.004, respectively). Low ERCC1 expression was also associated with longer OS (p = 0.003) while TS only showed a trend (p = 0.105). TS expression was independent predictor for the better PFS in multivariate analysis (hazard ratio [HR] = 0.32, 95% confidence interval [CI]: 0.14-0.76). Combining the two markers, the low TS/low ERCC1 group showed significantly longer PFS (HR = 0.48, 95% CI: 0.26-0.75) and OS (HR = 0.57, 95% CI: 0.36-0.89) compared with high TS/high ERCC1 group. Protein expressions of TS and ERCC1 were associated with clinical outcomes in patients with pulmonary adenocarcinoma who were treated with pemetrexed/cisplatin as first-line chemotherapy. TS and ERCC1 protein expressions can be potential predictive markers in this setting.