晚期非小细胞肺癌组织中ERCC-1、Metallothionein、p53表达与铂类耐药性及预后的相关性分析

Correlation Analysis among Expression of ERCC-1, Metallothionein, p53 and Platinum Resistance and prognosis in Advanced Non Small Cell Lung Cancer

背景与目的晚期非小细胞肺癌含顺铂方案化疗敏感性分子预测指标尚处于探索阶段。本研究分析晚期非小细胞肺癌石蜡包埋组织中错配切除修复蛋白(excisionrepaircrosscomplement-1,ERCC-1)、金属硫蛋白(metallothionein,MT)、p53蛋白与顺铂化疗敏感性的关系,并观察这些指标与病人生存的关系。方法收集1994年1月-2001年12月在本院经病理组织学诊断的用含铂方案(Gemzar+DDP或NVB+DDP)化疗的初治晚期非小细胞肺癌患者的病理标本,采用免疫组化方法检测ERCC-1、MT、p53的表达,并将病人的疗效和生存资料与上述指标的表达进行比较。样本率的比较用χ2检验,用Kaplan-meier法和Cox回归进行生存分析。结果本组51例标本中,ERCC-1阳性率为42.8%,MT阳性率为57.5%,p53阳性率为37.8%。化疗有效率在ERCC-1、MT、p53阴性组和阳性组分别为33.3%、35.3%、21.4%和16.7%、27.3%、35.3%(即分别为1.99倍,1.29倍,0.61倍),但均未达统计学差异(P>0.05),ERCC-1,MT均阴性组有效率为37.5%,均阳性组有效率为14.3%,前者为后者的2.6倍,但未达统计学差异(P>0.05)。平均生存期ERCC-1、MT、p53蛋白阴性组和阳性组分别为621.03天/523.14天,556天/479天,599.64天/416.60天。Kaplan-meier分析显示三者过度表达均提示预后不良,但Cox回归分析显示只?

BACKGROUND & OBJECTIVE: The molecular predictor for cisplatin sensitivity in advanced non small cell lung cancer (NSCLC) is still an open question at present. The purpose of this study was to evaluate the relationship of the cisplatin sensitivity/prognosis with the expression of excision repair cross complement 1 (ERCC 1), metallothionein (MT), and p53 in the paraffin embedded tissue of advanced non small cell lung cancer (NSCLC). METHODS: From January 1994 to December 2001, 51 pathologically confirmed advanced NSCLC patients were included. All patients received cisplatin contained regimen chemotherapy (Gemzar + DDP or NVB + DDP) as the first line treatment. At the same time, the tumor samples were collected and the expression of ERCC 1, MT, and p53 in the tumor samples were examined by immunohistochemical method. The response rates and survival data were analyzed according to the over expression or not of these three parameters (negative group/over expression group). The response rates were compared by χ2 test. Kaplan Meier method and Cox proportional hazards model were used for survival analysis. RESULTS: In these 51 patients, the expression rates of ERCC 1, MT, and p53 were 42.8%, 57.5%, and 37.8%, respectively. The response rates in negative group/over expression group of ERCC 1, MT, and p53 were 33.3%/16.7%, 35.3%/27.3%, and 21.4%/35.3%, respectively (1.99, 1.29, and 0.61 times, respectively, P >0.05). The response rate in both ERCC 1 and MT negative group was 37.5%. In both ERCC 1 and MT over expression (co expression) group, the response rate was 14.3%. The former was 2.6 times of the latter (P >0.05). The average survival time in negative group/over expression groups were 621/523 days (for ERCC 1), 556/479 days (for MT), 599/416 days (for p53), respectively. ERCC 1, MT, or p53 over expression group showed poorer prognosis than those of negative group by Kaplan Meier analysis. But in multivariate analysis, only p53 over expression was an independent poor prognostic factor of survival time (Cox regression, P=0.009). CONCLUSION: Whether over expression of ERCC 1 and MT can be used as a molecular marker of cisplatin resistance in advanced NSCLC patients need further study. Over expression of p53 predicates poor prognosis for patients with advanced NSCLC.