乳腺癌组织中四种耐药相关蛋白的表达及其临床意义

目的:研究包括P-糖蛋白(P-glycoprotein,PGP)、多药耐药相关蛋白-1(Multidrug resistance-associated protein1,MRP1)、肺耐药相关蛋白(Lung resistance-related protein,LRP)和乳腺癌耐药蛋白(Breast cancer resistance protein,BCRP)在乳腺癌组织中的表达,并评估其在乳腺癌预后中的作用。方法:采用免疫组织化学方法检测50例经手术切除的乳腺癌组织中PGP、MRP1、LRP和BCRP的表达,并分析其与临床、病理特征的关系及其对预后的影响。结果:(1)各种耐药蛋白在乳腺癌组织中均有不同程度的表达,PGP、MRP1、LRP和BCRP的表达率分别为82·0%(41/50)、86·0%(43/50)、80·0%(40/50)和58·0%(29/50);(2)除MRP1表达与淋巴结转移状况有关以及BCRP表达与激素受体有关外(P<0·05),PGP、MRP1、LRP和BCRP表达与月经状况、肿瘤大小、淋巴结转移、组织分级和激素受体状况均无关(P>0·05);(3)Kaplan-Meier生存分析结果表明PGP、MRP1、LRP和BCRP表达均与无病生存期明显相关(P<0·05),但只有PGP表达与总生存期显著相关(P<0·01),而MRP1、LRP和BCRP表达与总生存期无关(P>0·05);(4)Cox多因素分析中,肿瘤大小和腋淋巴结转移与无病生存期和总生存期明显相关(P<0·05),但PGP表达仅与总生存期明显相关(P<0·05)。结论:乳腺癌组织中具有多种耐药蛋白的过度表达,其中PGP有可能成为判断乳腺癌患者预后的独立指标。

The clinical significance of drug resistance-associated protein (DRP) expression in primary breast carcinoma

Objective:To investigate the expression of multidrug resistance gene production P-Glycoprotein (PGP),multidrug resistance-associated protein (MRP1), lung resistance-related protein (LRP), and breast cancer resistance protein (BCRP) in primary breast carcinoma, and to determine whether such the expression can predict survival.Methods:Expression of the four proteins in 50 breast cancer patients was determined by immunohiostochemistry on formalin-fixed, paraffin-embedded tumor section. The relationship between the expression of DRP and the clinicpathological characteristics, and the prognosis of breast cancer patients were also analyzed.Results:(1)PGP expression was observed in 41 of 50(82.0%),MRP1 in 43 of 50(86.0%),LRP in 40 of 50(80.0%),and BCRP in 29 of 50(58.0%)tumors. (2)MRP1 expression was more frequently observed in patients with lymph node metastasis(P<0.05), and did BCRP expression in patients with hormone receptor positive (P<0.05). No relation can be established between expression of PGP, MRP1, LRP, BCRP, and other clinicopathological parameters (P>0.05).(3) Kaplan-Meier analyses revealed that the four proteins were colsely associated with disease-free survival (DFS), however PGP expression also associated with overall survival (OS) (P<0.05) and didn't the other protein (P>0.05).(4)In multivariate Cox regression analyses, only tumor size and lymph node metastasis were independent prognostic factor for DFS and OS(P<0.05).In addition, PGP was independent prognostic factor for OS (P<0.01).Conclusion:Our results suggested that PGP, MRP1, LRP and BCRP were frequently expression in primary breast carcinoma, and PGP might be used as one of the markers for poor prognosis in patients with breast cancer.