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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
Author(s) -
TSEDENISH MANALJAV,
CHOI YOODUK,
CHO HYUNJU,
BAN HEEJUNG,
OH INJAE,
KIM KYUSIK,
SONG SANGYUN,
NA KOOKJOO,
AHN SUNGJA,
CHOI SONG,
KIM YOUNGCHUL
Publication year - 2012
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2011.02060.x
Subject(s) - ercc1 , medicine , vinorelbine , genotype , oncology , lung cancer , nucleotide excision repair , chemotherapy , gastroenterology , single nucleotide polymorphism , stage (stratigraphy) , surgery , dna repair , gene , biology , cisplatin , genetics , paleontology
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.