晚期非小细胞肺癌ERCC1和BRCA1的表达及与顺铂耐药性的临床研究

ERCC1 and BRCA1 expressions in advanced non-small cell lung cancer and their relationship with cisplatin resistance

目的:探讨核苷酸切除修复交叉互补组1(excision repair cross complementation group 1,ERCC1)和乳腺癌易感基因(breast cancer susceptibility gene 1,BRCA1)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及与顺铂耐药的关系。方法:应用免疫组织化学法检测81例NSCLC患者标本ERCC1和BRCA1蛋白的表达,并与患者年龄、性别、组织病理学类型、临床分期、吸烟指数及含铂化疗方案疗效的关系进行分析。结果:ERCC1蛋白表达阳性率为35.80%,与患者的性别、年龄、临床分期及吸烟指数无关,ERCC1蛋白在腺癌中的表达高于鳞癌,差异有统计学意义(P<0.05);ERCC1表达阳性组的化疗有效率(24.14%)低于阴性组(63.46%),差异有统计学意义(P<0.05);ERCC1表达阳性组的中位生存期(median sur-vival time,MST)(12.1个月)低于阴性组(20.6个月),差异有统计学意义(P<0.05)。BRCA1蛋白表达阳性率为51.85%,与患者的性别、年龄、临床分期、组织学类型及吸烟指数无关;BRCA1表达阳性组化疗有效率(38.10%)低于阴性组(61.54%),差异有统计学意义(P<0.05);BRCA1表达阳性组的MST(15.2个月)与阴性组(16.7个月)比较无明显差异。结论:ERCC1和BRCA1蛋白表达检测可预测NSCLC患者对铂类化疗药物的敏感性,有助于临床上NSCLC个体化化疗方案的制定。

Objective ： To investigate the excision repair cross complementation group 1 （ ERCC1 ） and breast cancer susceptibility gene 1 （ BRCA1 ） in advanced non-small cell lung cancer （NSCLC） and their relationship with cisplatin resistance. Methods：This study examined the ERCC1 and BRCA1 protein expression in 81 specimens from NSCLC patients by immunohistochemical staining method and analyzed the relationship between the ERCC1 and BRCA1 protein expressions and the patients＇ age, gender, pathological classification, clinical stage, smoking index, and the efficacy of cisplatin-based chemotherapy. Results： The positive rate of ERCC1 expression was 35.80% in 81 NSCLC patients, which had no correlation with the patients＇ age, gender, clinical stage, and smoking index. But its expression was higher in puhnonary adenocarcinoma than that in squamous carcinoma. The difference was significant （ P 〈 0.05 ）. The response rate of ERCC-positive patients to cisplatin-based chemotherapy was 24.14%, significantly lower than that in ERCC-negative patients （63.46%）. There was a significant difference between the two groups （P 〈0.05）. The median survival time （MST） of ERCC- positive patients was shorter than ERCC-negative patients （ 12.1 vs 20.6 months）. The difference was significant （P 〈 0.05 ）. The positive expression rate of BRCA1 was 51.86% , which had no correlation with the patients＇ gender, age, clinical stage, and histological classification, and smoking index. The response rate of BRCAl-positive patients to platinum-based chemotherapy was 38.10%, significantly lower than that of BRCA1 -negative patients （61.54%）. There was a significant difference between the two groups （P 〈 0.05 ）. There was no significant difference in MST between the two groups （ 15.2 vs 16.7 months）. Conclusion：The detection of ERCC1 and BRCA1 expression could be used to predict the sensitivity of NSCLC patients to cisplatin-based chemotherapy and help to design individual therapeutic regimen for advanced NSCLC patients in clinic.