拓扑异构酶Ⅱα和Ki-67的表达对Ⅰ~Ⅲ期非小细胞肺癌术后辅助化疗疗效的预测意义*

Expression of Topoisomerase IIα is Predictive of Response to Adjuvant Chemotherapy in Stage I-III Non-Small Cell Lung Cancer Patients after Surgical Treatment

  • 摘要: 目的:探讨TopⅡα 和Ki-67在NSCLC 中的表达情况,并评价上述2 项指标对接受辅助化疗的NSCLC 患者的预后及预测价值。方法:收集2004年1 月至2007年12月在解放军总医院接受手术治疗且术后行至少1 个周期辅助化疗且随访资料完整的Ⅰ~Ⅲ期NSCLC 病例共152 例。利用免疫组化法检测上述病例中TopⅡα 和Ki-67的表达,分析其表达特点和全组病例的临床病理特征、治疗特征、分子特征与生存规律的关系。结果:TopⅡα 与Ki-67的过表达率分别为22.4% 和36.2% ,两者表达中度相关(r=0.516,P<0.001),且其表达程度与年龄、性别、吸烟状况、病理类型及临床分期等无关。截至末次随访2009年4 月1 日,41例死亡,中位生存期未达到,中位DFS 为23.0 个月。单因素分析显示男性(P=0.041)、临床分期早(P=0.001)、N 分期早(P<0.001)、非腺癌(P=0.003)及TopⅡα 高表达者(P=0.011)较女性、临床分期晚、N 分期晚、腺癌及TopⅡα 低表达者中位DFS 显著延长,而年龄、吸烟与否、化疗方案的类型及Ki-67的表达程度对DFS 无显著影响。分层分析发现,TopⅡα 低表达时含NVB 方案组较其他方案DFS有明显延长趋势(P=0.059);Ki-67低表达时,NVB 组中位DFS 显著高于TXT 组(P=0.032)。 而在TopⅡα 或Ki-67高表达时,各化疗方案组对DFS 的影响亦无明显差异。COX 多因素分析显示,腺癌与否、N 分期及TopⅡα 表达程度均是影响DFS 的独立预后因素。结论:对于接受手术治疗的NSCLC 患者,TopⅡα 高表达者较低表达者更能从辅助化疗中获益;且在TopⅡα 低表达时,使用含NVB 的化疗方案较其他常用方案似乎能给患者带来更好的收益。而Ki-67的表达对DFS 却无类似预测价值;但在Ki-67低表达时,含GEMZ 和PTX 方案,特别是含NVB 方案可能较TXT 有更好的疗效。TopⅡα 可能成为判断NSCLC 辅助化疗疗效及筛选化疗药物的新预测指标。

     

    Abstract: Objective: To determine the predictive values of Top II α and Ki67expression in postoperative stage I-III non-small lung cancer patients who received adjuvant chemotherapy. Methods:Non-small cell lung cancer cases who re-ceived surgical therapy in our hospital between January 2004and December 2007were analyzed. Cases with no follow up or who couldn’t finish at least one cycle of adjuvant chemotherapy were not recruited. Paraffin-embedded samples of 152 cases were col lected for immunohistochemical detection of Top II α and Ki67expression.Results: The expression rates of Top II α and Ki67were22.4% and 36.2% , respectively. Top II α expression was posi tively correlated wi th Ki67expression (r= 0.516 , P<0.001 ). By the end of the study, 41patients had died. The overall survival (OS) was not available. The median dis -ease free survival (DFS) was 23.0 months. In univariate survival analysis, sex, clinical stage, N stage, adenocarcinoma and expression level of Top II α were related to DFS, whi le age, smoking, chemotherapy regimens and expression level of Ki67 were of no prognostic significance. Factors indicating better DFS were male gender (P=0.041 ), earlier clinical stage ( P=0.001 ) or N stage (P<0.001 ), nonadenocarcinoma (P=0.003 ) and over-expression of Top II α (P=0.011 ). We further strati-fied for expression levels of Top II α and Ki67. In weak expression of Top II α strata, the regimen wi th NVB had prolonged DFS compared with the other regimens, but there was no statistical significance (P=0.059). And in weak-expression of Ki 67strata, the regimen with NVB had prolonged DFS compared with TXT regimen (P=0.033 ). However, there was no simi-lar prognostic signi ficance in over-expression of Top II α or Ki67strata. In COX proportional regression, presence of N stage adenocarcinoma and expression level of Top II α were independent risk factors affecting the prognosis of DFS. Conclusion: Over-expression of Top II α contributes to DFS of postoperative NSCLC patients who received adjuvant chemotherapy. The regimen wi th NVB is more effective than other regimens in improving DFS in weak-expression of the Top II α group, where-as the regimen with TXT is less effective than others in weak-expression of the Ki67group. Top II α can be considered as a new biomarker to predict the effect of adjuvant chemotherapy and is helpful for the selection of a better chemotherapy regi-men for postoperative NSCLC patients.

     

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