肾癌对化疗药物的多种耐药机制及其意义的研究

Mechanisms of drug resistance of primary renal cell carcinomas and their clinical significance

目的 通过多因素分析 ,研究肾癌多药耐药机制 ,为临床提高化疗有效率提供参考。方法 应用免疫组化的方法 ,对肾癌的主要耐药指标P糖蛋白 (P gp)、谷胱甘肽S转移酶π(GST π)、DNA拓扑异构酶Ⅱ (TopoⅡ )进行检测。结果 6 5 7%癌组织有P gp表达 ,高分期癌表达较低分期癌强。41 4%癌组织有GST π表达 ,表达强度与分级、分型、分期无关。 10 0 %的癌组织有不同程度的TopoⅡ表达。 70例中表达 1种耐药指标者 (P gp阳性、GST π阳性或TopoⅡ <10 0 )占 31 4% ,同时表达2种耐药指标者占 42 8% ,3种耐药指标者占 2 2 9% ,2例无耐药指标表达 ,三者之间存在相关关系。结论 P gp、GST π、TopoⅡ分别介导不同的药物耐药 ,选择P gp、GST π低表达同时TopoⅡ高表达的患者 ,并且针对不同MDR机制采用不同的化疗药物进行化疗 ,将有助于提高化疗有效率。

Objective By multifactorial analysis, to study the mechanisms of drug resistance of primary renal cell carcinomas (RCC). Methods Seventy cases of paraffin embedded RCC tissue sections were examined for the expression of P gp, GST π and TopoⅡ by immunohistochemical staining. Results There was 65.7% of RCC with expressed P gp. Its Expression was stronger in late than in early stage of RCC. GST π was expressed in 41.1% RCC, but the magnitude of expression did not correlate with differentiation, type and stage of RCC. All the RCC examined had TopoⅡ expression. Its expression level was lower than that of cancer of the intestine and lung. Among the 70 cases of RCC, 31.4% of them expressed at least one of the 3 drug resistance parameters. Co expression of two drug resistance parameters was observed in 42.8% of the cases that of 3 drug resistauce parameters in 22.9% of the cases. Conclusion Drug resistance is of common occurrence in RCC. To achieve better therapeutic efficacy, appropriate chemotherapeutic agents should be given to patients with low expression of P gp and GST π but high expression of TopoⅡ. Subject