Disease-free survival of patients after surgical resection of non-small cell lung carcinoma and correlation with excision repair cross-complementation group 1 expression and genotype

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Background and objective:Expression of excision repair cross-complementation group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who have undergone surgical resection of non-small cell lung cancer (NSCLC). However, in patients treated with adjuvant chemotherapy after surgical resection, ERCC1 correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to be a predictive marker of the efficacy of treatment with taxanes or vinorelbine.Methods:Tumour tissues (n= 363) from patients with surgically resected NSCLC were analysed retrospectively. Tissue sections were labelled with ERCC1- and TUBB3-specific antibodies. Using genomic DNA from 262 patients, single nucleotide polymorphisms of the ERCC1 gene (T19007C and C8092A) were genotyped by PCR-restriction fragment length polymorphism analysis.Results:Only 5.9% of patients with stage I disease (14/238) and 61.6% of patients with stages II–III disease (77/125) received adjuvant chemotherapy. Relapses were noted in 30.6% (111) of patients, and among these, 31 ultimately succumbed. The relapse rate (RR) was 24.8% for stage I disease, and 41.6% for stages II–III disease. The RR was significantly lower in ERCC1-positive (24.3%) as compared with ERCC1-negative patients (36.3%,P= 0.014) and was lower in patients with the AA/CA genotype at the ERCC1 C8092A locus (29.5%) compared with those with the CC genotype (42.1%,P= 0.034). The median disease-free survival (DFS) time was 62.3 months. DFS was significantly greater in ERCC1-positive patients (62.3 months) than in ERCC1-negative patients (48.0 months,P= 0.042). In a multivariate analysis, ERCC1 expression and the C8092A polymorphism were independent prognostic factors in patients with stage I disease who were naïve to chemotherapy.Conclusions:ERCC1 expression and the AA/CA genotype at the C8092A locus were correlated with a good prognosis in patients who had undergone surgical resection of NSCLC.

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