肺癌组织中P-gp、MRP、p53蛋白的表达及其临床意义

Expressions of P-gp, MRP and p53 Protein and Their Clinical Significance in Human Lung Cancer Tissues

目的探讨P-糖蛋白、多药耐药相关蛋白、p53蛋白在肺癌中可能的临床意义及相互间的关系。方法采用免疫组化法检测31例石蜡包埋的肺癌及相应远离肿瘤部位的正常肺组织中P-糖蛋白、多药耐药相关蛋白、p53蛋白的表达情况,同时用流式细胞术检测其中29例冻存的肺癌组织中P-糖蛋白、p53蛋白水平,并与免疫组化法结果比较。结果免疫组化法显示P-糖蛋白、多药耐药相关蛋白、p53蛋白在正常肺组织中未见表达,在肺癌组织中阳性率分别为61.3%、54.8％、71.O％。P-糖蛋白与多药耐药相关蛋白表达有相关性(P<0.01),但P-糖蛋白与p53蛋白,多药耐药相关蛋白与p53蛋白之间均无相关性。P-糖蛋白和多药耐药相关蛋白阳性集中在非小细胞肺癌,阳性率分别为76％、68％,且肺癌细胞分化程度越低,P-糖蛋白阳性率越低(P<0.05)。p53蛋白阳性率在鳞癌(100％)明显高于腺癌(33.3％)(P<0.01),吸烟患者(88.9％)明显高于不吸烟患者(46.2%)(P<0.05),而与P-TNM各项指标无关。采用流式细胞术测得P-糖蛋白、p53蛋白阳性率分别为65.5％、79.3％,两种方法的符合率在P-糖蛋白、p53蛋白分别为62.1％、75.9％。结论P-糖蛋白、多药耐药相关蛋白过表达在肺癌中可能具有一定的协同作用,而与p53蛋白异常无关。

Objective To investigate the clinical role of P-gp, MRP and p53 protein in primary lung cancer and their relationship with each other. Methods P-gp, MRP and p53 protein were measured in 31 paraffin-embedded lung cancer and corresponding normal lung tissues by immunohistochemistry(IHC) . In addition, we performed flow cytometric analysis of P-gp and p53 protein in 29 of 31 frozen lung cancer specimens in order to compare the results of the two methods. Results By IHC, positive rates of P-gp, MRP and p53 protein were 61.3%, 54.8%, 71.0% respectively in 31 lung cancer cases and there was no expression in all normal lung tissues. P-gp and MRP expressed only in NSCLC. The poorer the cancer cell differentiated, the lower the positive rate of P-gp expression was ( P < 0.05) . Squamous cell carcinomas showed much higher positive rate of p53 protein than adenocarcinomas ( P < 0.01). As compared with the non-smokers, staining for p53 overwhelmingly positive in the smokers ( P < 0.05) . Neither P-gp nor MRP had significant correlation with p53 protein, however, coexpression of P-gp and MRP had a distinct statistic significance (P<0.01),the expression rates of P-gp and MRP had a distinct statistic significance (P < 0.01) . By flow cytometry (FCM), the expression rates of P-gp and p53 protein were 65.5% , 79.3% in 29 lung cancer cases. The coincident rates of P-gp and p53 protein by IHC and FCM were 62.1 % , 75.9% respectively. Conclusion P-gp and MRP overexpression may be involved in the process of lung cancer in coordination. Neither P-gp overexpression nor MRP overexpression has significant correlation with p53 alteration.