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

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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.

Original languageEnglish
Pages (from-to)102-108
Number of pages7
JournalLung Cancer
Volume81
Issue number1
DOIs
Publication statusPublished - 2013 Jul 1

Keywords

  • Chemotherapy
  • ERCC1
  • Predictive marker
  • Pulmonary adenocarcinoma
  • Thymidylate synthase

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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