乳腺癌干细胞含量及其耐药相关蛋白表达的临床病理意义  

Clinicopathologic significance of breast cancer stem cells concerning their content and expression of drug resistance related proteins

作　　者：韩玉贞[1] 桑晶[2] 吕增华[3] 朱玉红[3] 

机构地区：[1]滨州医学院病理学教研室,山东滨州256603 [2]山东省泰安市中心医院病理科,山东泰安271000 [3]滨州医学院附属医院病理科,山东滨州256603

出　　处：《中国普通外科杂志》2012年第11期1389-1393,共5页China Journal of General Surgery

基　　金：山东省医药卫生科技发展计划资助项目(2009HZ001)

摘　　要：目的:探讨乳腺癌中癌干细胞含量与临床病理参数的关系,以及P-糖蛋白(P-gp),谷胱甘肽S转移酶π(GST-π),肺耐药蛋白(LRP)和拓扑异构酶II(TOPO-Ⅱ)在乳腺癌干细胞和分化细胞中的表达及其意义。方法:选取乳腺浸润性导管癌新鲜标本30例制备成单细胞悬液,通过免疫磁珠两步法从中分离出癌干细胞(CD44+/CD24-细胞)和分化细胞(CD24+和CD44-CD24-细胞)并计数,分析癌干细胞含量与乳腺癌患者临床病理参数的关系;应用免疫细胞化学方法检测以上两种细胞P-gp,GST-π,LRP和TOPO-Ⅱ的表达情况。结果:乳腺癌干细胞含量与患者的年龄、肿块大小、组织学分级及淋巴结转移均无明显关系(均P>0.05)。乳腺癌干细胞P-gp的阳性表达率明显高于分化细胞(73.3%vs.40.0%),而TOPO-Ⅱ的阳性表达率明显低于分化细胞(40.0%vs.76.7%)(P<0.05或P<0.01);GST-π和LRP的表达在两种细胞间无统计学差异(均P>0.05)。结论:乳腺癌干细胞含量与患者的临床病理参数无关,但乳腺癌干细胞中P-gp高表达与TOPO-Ⅱ低表达可能是导致乳腺癌化疗失败和复发的重要原因。Objective： To investigate the relationship between the content of cancer stem cells and clinicopathologic parameters of the patients with breast cancer, and the expressions and significances of P-glycoprotein （P-gp）, glutathione S-transferase-π （GST-π）, lung resistance protein （LRP） and topoisomerase II （TOPO-II） in breast cancer stem cells and differentiated breast cancer cells. Methods- Fresh tumor tissues from 30 invasive ductal carcinoma patients were mechanically dissociated into single cell suspensions, from which the cancer stem cells （CD44^＋/CD24^- cells） and differentiated cancer cells （CD24^＋ and CD44^-CD24^- cells） were separated by two-step immunomagnetic sorting procedure and then counted. The relations of the content of cancer stem cells with the clinicopathologic variables of the patients were analyzed. The expressions of P-gp, GST-π, LRP and TOPO-II in the above two cells were determined by immunocytochemical staining. Results： The content of breast cancer stem cells was not clearly related to the age, tumor size, histological grade and lymph node metastasis of the patients （all P〉 0.05）. Compared with differentiated cancer cells, the positive expression rate of P-gp was significantly elevated （73.3% vs. 40.0%） but TOPO-II was significantly decreased （40.0% vs. 76.7%） in breast cancer stem cells （P〈0.05 or P〈0.01）. while the expressions of GST-π and LRP in the two types of cells showed no significant difference （both io〉0.05）. Conclusion： The content of cancer stem cells is not clearly associated with clinicopathologic parameters of breast cancer patients. However, breast cancer cells may contribute to chemotherapy resistance and recurrence of breast cancer due to their increased P-gp and decreased TOPO-II expression.

关 键 词：乳腺肿瘤 肿瘤干细胞 多药耐药相关蛋白质类 

分 类 号：R737.9[医药卫生—肿瘤]