ERCC1 AND PLATINUM THERAPY

Lung Cancer. 2009 Jan 15. [Epub ahead of print]

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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.

Lee HW, Choi YW, Han JH, Kim JH, Jung JH, Jeong SH, Kang SY, Choi JH, Oh YT, Park KJ, Hwang SC, Sheen SS.

Department of Hematology-Oncology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea; Lung Cancer Center, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.

BACKGROUD: 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.