P-gp、MRP、LRP、P53及c-erbB-2在非小细胞肺癌中的表达

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.

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

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 <0.001,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,<(0.001,) <0.001 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).) Conclusion: Overexpression of P-gp,MRP,LRP,P53 and c-erbB-2 may play a cooperative role in the drug resistance and development of NSCLC.