ERCC1、RRM1和p53表达与Ⅰ-Ⅱ期肺癌术后预后相关性分析

Prognostic Analysis of ERCC1, RRM1 and p53 Expressions in Postoperative Stage Ⅰ-Ⅱ Lung Cancer

背景与目的顺铂是肺癌化疗的基础药物,而ERCC1、RRM1、p53表达水平与铂类耐药和预后有关,本研究分析Ⅰ-Ⅱ期NSCLC的ERCC1、RRM1、p53表达与术后生存期的关系,探讨它们与患者预后及与顺铂耐药的相关性。方法收集1992年2月-l994年1月有随访的75例Ⅰ-Ⅱ期NSCLC术后患者,Ⅰ期术后随机分成不化疗组和化疗组,Ⅱ期术后均作化疗,化疗采用以DDP为基础的方案。免疫组化法检测手术标本的ERCC1、RRM1、p53表达,并进行统计分析。结果Ⅰ期ERCC1高表达患者预后明显好于ERCC1低表达,1、3、5年生存率分别为100.00%、91.30%、86.74%和96.43%、60.71%、57.14%(P=0.0058)。Ⅰ期不化疗组ERCC1高表达者生存情况优于ERCC1低表达,中位生存期(MST)分别为72.00+个月和64.67个月(P=0.0327)。Ⅱ期与Ⅰ期相反,ERCC1低表达者预后好,ERCC1低表达者的MST为60.00+个月,而高表达者仅为25.50个月(P=0.0442)。RRM1、p53表达与术后生存率无关。结论ERCC1高表达是Ⅰ期NSCLC术后预后良好的独立指标;含DDP化疗延长了Ⅱ期ERCC1低表达患者的生存,术后可根据ERCC1的水平决定是否选用含DDP化疗;ERCC1表达对NSCLC术后生存期的影响在Ⅰ期和Ⅱ期DDP化疗患者中可能不尽相同,ERCC1高表达在Ⅰ期NSCLC术后展现的是其保护的一面,而Ⅱ期以化疗抵抗为主。

Background and objective Cisplatin is an important drug in lung cancer chemotherapy. It has been proven that ERCC1, RRM1, p53 expressions were related to resistance to platinum and prognosis of the patcents with lung cancer. The aim of this study is to analyze the association of the expression of ERCC1, RRM1, p53 with postoperative survival in patients with stage Ⅰ - Ⅱ non-small-cell lung cancer （NSCLC）, and to explore the relationship between the expression of ERCC 1, RRM1, p53 and resistance to cisplatin. Methods A total of 75 patients with stage Ⅰ - Ⅱ NSCLC receiving radical resection from Feb. 1992 to Jan. 1994 were followed up. Postoperative patients with stage Ⅰ were randomized two groups （chemo and non-chemo groups）. All patients with stage Ⅱ received adjuvant cisplatinbased chemotherapy. Immunohistochemical staining was used to detect the expression of ERCC1, RRM1, p53 in paraffinembedded specimens. Results In stage I NSCLC, the prognosis of the patients with high expression of ERCC1 （High-ERCC 1） was better than those with low expression of ERCC 1 （Low-ERCC 1）. 1, 3, 5-year survival rate in the patients with high expression of ERCC 1 was 100.00%, 91.30%, 86.74% and in those with Low-ERCC 1 was 96.43%, 60.71%, 57.14%, respectively （P=0.0058）. The patients with High-ERCC1 had a better survival rate than those with Low-ERCC1 in stage I NSCLC without chemotherapy. MST in high and low expression of ERCC1 was 72.00^＋ months and 64.67 months, respectively （P=0.0327）. In contrary to stage Ⅰ NSCLC, the patients with had a better survival rate than those with in stage Ⅱ. MST was 60.00^＋ months in stage 11 patients with low expression of ERCC1, but MST was only 25.50 months with （P=0.0442）. The postoperative survival of NSCLC patients was not any statistical different between with high expression and low expression of RRM1 and p53. Conclusion High expression of ERCC1 is a better independent prognostic factor in stage Ⅰ NSCLC patients. Cisplatin-base chemotherapy prolongs survival in stage Ⅱ NSCLC patients with. Adjuvant chemotherapy regimen is determined according to ERCC 1 expression levels in resected NSCLC.