الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Although current treatment option for advanced non–small-cell lung cancer (NSCLC) relies on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 expression (both protein and mRNA) would improve response and survival.
Patients and methods: from March 2009 to April 2010, 61 chemotherapy naïve stages IIIB and IV NSCLC patients were enrolled. ERCC1 protein and mRNA expression was detected from pretreatment biopsies by Immunohistochemistry and real-time quantitative PCR assays, respectively. Patients received cisplatin based regimen in the form of cisplatin plus ( etoposide or gemcitabine or docetaxel or vinorelbine).The primary end point was the impact of ERCC1 expression on PFS and OS.
Results: All biopsy specimens (61) were candidate for mRNA detection; 31 patients (50.8%) showed positive ERCC1 expression while only 52 biopsy specimens were candidate for protein detection; 34 patients (65.4%) showed positive ERCC1 expression. Complete concordance among the RT-QPCR and IHC for detection of ERCC1 expression was detected in 38 out of the 52 cases (73%). Positive ERCC1 expression was associated with short PFS (P < 0.001 for mRNA and P = 0.001 for protein). Positive ERCC1 expression was associated with short OS (P = 0.001 for mRNA and P = 0.003 for protein). Also, positive ERCC1 expression was associated with poor response to cisplatin based chemotherapy (P < 0.001 for mRNA and P = 0.027 for protein).
Conclusions: This prospective study further validates ERCC1 as a reliable biomarker for customized chemotherapy in advanced NSCLC patients and shows that high expression of ERCC1 by IHC or RT-PCR was significantly associated with poor outcome in advanced NSCLC patients treated with platinum based chemotherapy.