非小细胞肺癌多药耐药性病理学检测的临床意义.DOCVIP

临床医学论文-非小细胞肺癌多药耐药性病理学检测的临床意义 【摘要】? 目的 检测113例非小细胞肺癌（NSCLC）中谷胱甘肽巯基转移酶π（GSTπ）、肺耐药相关蛋白（LRP）、DNA拓扑异构酶Ⅱa（TopoⅡa）、多药耐药相关蛋白（MRP）和多药耐药基因（MDR1）的表达，观察上述指标与肿瘤临床病理因素的关系及各指标表达之间的相关性。方法 采用免疫组化SP法检测GSTπ、LRP、TopoⅡa蛋白的表达；应用原位杂交技术检测MRP和MDR1 mRNA表达。结果 (1)GSTπ、LRP、TopoⅡa蛋白及MRP、MDR1 mRNA在113例NSCLC中的阳性表达率分别为75.2%、80.5%、60.2%、79.6%、51.3%。其中LRP表达最高，MDR1表达最低。(2)LRP、TopoⅡa和MRP的表达分别与肿瘤组织学类型有关。(3)GSTπ与MRP（P＜0.05）、LRP与MRP（P＜0.01）、MDR1与MRP（P＜0.01）的表达间具有相关性。结论 (1)多种耐药相关基因的过度表达及其相互作用可能是NSCLC产生原发MDR的重要原因。(2)LRP和MRP过度表达，TopoⅡa高表达和MRP低表达可能分别与肺腺癌、鳞癌的化疗敏感性有关。 【关键词】? 非小细胞肺癌; 多药耐药; 免疫组化; 原位杂交 　　　Abstract：Objective?? To evaluate the expressions of GSTπ, LRP, TopoⅡa, MRP and MDR1 in 113 nonsmall cell lung cancer(NSCLC), to observe their relationships with clinicopathologic characterization of cancer and their interactions.Methods? Expressions of GSTπ, LRP and TopoⅡa were detected by SP immunohistochemistry, and expressions of? MRP, MDR1 mRNA in paraffinembedded cancer tissues were detected by in situ hybridization.Results? (1)The positive rates of GSTπ, LRP, TopoⅡa and MRP, MDR1 mRNA were 75.2%, 80.5%, 60.2%,79.6% and 51.3% in NSCLC, respectively.(2)The expressions of LRP, TopoⅡa, MRP had a close relationship with the histological types in NSCLC, respectively.(3)There were significant relationships between positive rates of GSTπ and MRP(P＜0.05), LRP and MRP(P＜0.01), MDR1 and MRP(P＜0.01), respectively.Conclusion? (1)The overexpressions and interactions of GSTπ, LRP, TopoⅡa, MRP and MDR1 are important causes of primary MDR in NSCLC. (2)The overexpressions of LRP and MRP, the overexpression of TopoⅡa and the reduced expression of MRP, which are related with the chemotherapeutic sensitivity in adenocarcinoma and squamous carcinoma, respectively. 　　Key words：Nonsmall cell lung cancer; Multidrug resistance; Immunohistochemisty; In situ hybridization 　　0? 引言 ??? 多药耐药是指肿瘤对一种化疗药物出现耐药的同时，对其他许多结构不同、作用机制各异的化疗药物亦产生交叉耐药的现象。与小细胞肺癌相比，非小细胞肺癌（NSCLC）的联合化疗有效率较低，其耐药性更为突出。本研究采用免疫组化和原位杂交技术，对NSCLC组织中5种多药耐药相关蛋白或mRNA的表