P-gp、MRP、LRP、P53及c-erbB-2在非小细胞肺癌中的表达

Expression of P-glycoprotein,multidrug resistance associated protein,lung resistance-related protein,P53 and c-erbB-2 in non-small cell lung cancer

目的:探讨P糖蛋白(P-gp)、多药耐药相关蛋白(MRP)、肺耐药蛋白(LRP)、P53蛋白及c-erbB-2蛋白在术前未经治疗的非小细胞肺癌(NSCLC)中的表达及相互间的关系。方法:采用免疫组化法检测78例NSCLC癌组织及15例癌旁肺组织(距癌灶5 cm)中P-gp、MRP、LRP、P53及c-erbB-2的蛋白表达情况。结果:免疫组化显示P-gp、MRP、LRP、P53及c-erbB-2在肺癌组织中的阳性表达率分别是65.4%(51/78)、39.7%(31/78)、56.4%(44/78)、53.8%(42/78)及43.6%(34/78),均显著高于癌旁肺组织中的表达水平(P<0.05);MRP和LRP蛋白表达在不同病理类型(腺癌、鳞癌及大细胞癌)之间比较均具有显著性差异(P分别为0.008和<0.001),LRP及P53蛋白表达在不同病理分化程度之间具有显著性差异(P分别为0.025和0.026);c-erbB-2表达与P-gp、MRP、LRP、P53均有相关性(Spearman相关系数分别为0.317、0.401、0.519和0.341,P值分别为0.005、<0.001、<0.001和0.002),P53与MRP之间(Spearman相关系数为=0.260,P=0.022)以及LRP与MRP之间(Spearman相关系数为0.371,P=0.001)有相关性。结论:P-gp、MRP、LRP、P53及c-erbB-2这些蛋白的表达在NSCLC的多药耐药形成及肿瘤的发生发展中可能具有一定的协同作用。

Objective：To investigate the expression of P-glycoprotein （P-gp）, multidrug resistance-related protein （MRP）, lung resistance-related protein （LRP）, P53 and c-erbB-2 in untreated non-small cell lung cancer （NSCLC） and their relationship with each other. Methods： The expression of P-gp, MRP, LRP, P53 and c-erbB-2 was detected in the carcinoma tissues of 78 NSCLC patients and 15 adjacent normal lung tissues （5 cm apart from tumors） by means of immunohistochemistry. Results： The positive rates of P-gp, MRP, LRP, P53 and c-erbB-2 in tumor tissues were 65.4 %, 39.7 %, 56.4 %, 53.8 % and 43.6 %, respectively, all significantly higher than those in normal tissues（P〈0.05）. There was also significant difference in MRP and LRP expression between different pathologic types of NSCLC（squamous cell carcinoma, adenocarcinoma, large cell carcinoma） （P= 0. 008 and G0. 001, respectively）. Expression of LRP and P53 was also significantly different between different degrees of pathological differentiation （well, moderate, poor） （P=0. 025 and 0. 026, respectively）. The expression of c-erbB-2 was correlated with those of P-gp, MRP, LRP and P53 （Spearman R=0. 317, 0. 401, 0. 519 and 0. 341, respectively;P=0. 005, G 0. 001, G0.001 and =0.002, respectively） ; the expression of P53 was correlated with that of MRP （Spearman R=0. 260,P= 0. 022） ; and the expression of LRP was correlated with that of MRP （Spearman R = 0. 371, P= 0. 001 ）. Conelusion： Overexpression of P-gp, MRP, LRP, P53 and c-erbB-2 may play a cooperative role in the drug resistance and development of NSCLC.