乳腺癌组织耐药相关蛋白的表达及其临床意义

Expression of drug resistance related genes in breast cancer tissues and its clinical significance

目的:探讨乳腺癌组织耐药相关基因表达及其与临床病理学因素之间的关系。方法:应用流式细胞术检测多药耐药蛋白P-糖蛋白(P-gP)、谷胱苷肽-S-转移酶(GST-π)、肺耐药蛋白(LRP)、多药耐药相关蛋白(MRP)和O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)在64例乳腺癌组织中的表达情况,分析其与患者临床分期、年龄、肿瘤大小、腋窝淋巴结转移、雌孕激素受体(ER、PR)表达状态等因素的关系及5种耐药基因间的相关性。结果:P-gp、GST-π、LRP、MGMT和MRP在原发性乳腺癌组织中均有一定水平表达,P-gp和GST-π的表达与腋窝淋巴结转移有关(P值分别为0.007和0.031),MG-MT的表达在年龄<50岁组明显升高,P=0.018。GST-π、MRP和MGMT的表达在肿瘤体积较大组中明显升高(P值分别为0.042、0.000和0.015),5种耐药基因的表达与ER、PR表达相关差异均无统计学意义,P>0.05。乳腺癌组织中各耐药基因之间存在共表达现象,P-gp和GST-π的表达及LRP与MRP的表达均存在正相关性(r=0.66,P=0.000;r=0.434,P=0.004)。结论:乳腺癌组织中耐药蛋白的表达与患者肿瘤体积、年龄、淋巴结转移状况有关,耐药蛋白高表达,均提示为乳腺癌的不良预后指标。乳腺癌组织中各耐药蛋白之间存在共表达现象。

OBJECTIVE：To explore the mechanisms of drug resistance in breast cancer patients and the clinical biological datas. The correlations among five kinds of multidrug resistance （MDR） related markers were also analyzed. METHODS.. The expressions of P-glycoprotein （ P-gP）, Glutsthione-S-transferases-π （GST-π）, multidrug related protein（MRP）, O^6-methyl-guanineDNA methyltransferase （MGMT） and lung resistance protein （LRP） were studied in 64 samples of breast cancer by flow cytometry and their clinical significance was analyzed by SPSS 10. 0. RESULTS： There were expressions of P-gp, GST-π, LRP, MGMT,MRP in breast cancer tissues. The expressions of P-gP and GST-π were higher in petients with lymph node metastasis （P = 0. 007 and P= 0. 031, respectively）. The expression of MGMT was higher in patients of ages 〈50, P = 0. 018. The levels of GST-π, MRP and MGMT were higher in patients with larger tumor size （P = 0. 042, 0. 000 and 0. 015, respectively）. The expressions of five kinds of MDR genes had no significant differences between estrogen receptor（ER） positive and ER negative groups and also between progesten receptor（PR） positive and PR negative groups. Among five kinds of MDR related markers, there were positive correlations between P-gP and GST-π expressions and between LRP and MRP expressions （r= 0. 66, P= 0. 000, r = 0. 434, P = 0. 004, respectively）. CONCLUSIONS The expressions of drug resistance proteines in breast cancer tissues are related to larger tumor size, age 〈50, lymph node metastasis, which may suggests that the higher expression of MDR genes may be a poor prognostic factor in breast cancer patients. There are coexpressions among five kinds of MDR related proteins.