Expression of excision repair cross-complementation group 1 protein predicts poor outcome in advanced non-small cell lung cancer patients treated with platinum-based doublet chemotherapy.

BACKGROUND

Alterations in apoptosis and DNA damage repair related proteins are associated with resistance to chemotherapy, which is the most important cause of treatment failure in advanced non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS

Pretreatment tumor biopsy specimens from 50 patients with NSCLC including stage IIIB with malignant pleural effusion or stage IV or recurrent disease were analyzed for p53, Bcl-2, Bax, and ERCC1 expression by immunohistochemistry. All patients were treated with platinum-based third-generation doublet chemotherapy, in which gemcitabine and cisplatin was the most commonly administered regimen (17 patients).

RESULTS

High expression of p53, Bcl-2, Bax, and ERCC1 was observed in 24 (48%), 8 (16%), 32 (63%), and 28 (55%) patients, respectively. In univariate analysis, high expression of ERCC1 demonstrated a trend of association with poor overall survival (OS) (median, 8 months vs. 11 months; P=0.055). High expression of p53, Bcl-2, Bax was not correlated with patient outcome. High expression of ERCC1 was an independent prognostic factor for poor OS (P=0.002) along with poor performance status (P=0.028) and lack of disease control (P=0.001) in multivariate analysis.

CONCLUSIONS

High expression of ERCC1 may be a useful prognostic factor for poor outcome in advanced NSCLC patients treated with platinum and third-generation doublet chemotherapy.