Cripto-1蛋白在乳腺癌中的表达和预后意义  

The Expression of Cripto-1 and Its Prognostic Significance in Breast Cancer

作　　者：雷婷[1] 郭晓静[1] 王欣欣[1] 范宇[1] 郎荣刚[1] 赵晶[1] 杨壹玲[1] 谷峰[1] 付丽[1] 

机构地区：[1]乳腺癌防治教育部重点实验室天津市肿瘤防治重点实验室天津医科大学附属肿瘤医院乳腺病理研究室,天津市300060

出　　处：《中国肿瘤临床》2010年第12期665-668,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:30930038,30600225);教育部长江学者乳腺癌创新团队奖励计划(编号:IRT0743);国家863重大项目(编号:2006AA02A249);国家973重大项目资助(编号:2009CB521700)~~

摘　　要：目的:研究具有促进上皮间质转化作用的Cripto-1蛋白在乳腺癌中的表达及意义。方法:采用免疫组织化学LSAB法检测205例乳腺癌标本中Cripto-1、E-cadherin(E-CD)及β-catenin的表达,并分析Cripto-1蛋白与E-CD及β-catenin的关系,同时分析Cripto-1蛋白与临床病理学特征、复发转移及生存时间的关系。结果:Cripto-1蛋白表达于癌细胞质,阳性表达率为82.9%(170/205),其表达与病理组织学分期(r=0.418,P=0.000)、HER2/neu(r=0.223,P=0.001)、淋巴结转移个数(r=0.293,P=:0.000)、淋巴结外软组织癌浸润(r=0.206,P=0.003)、肿瘤远处转移(r=0.273,P=0.000)呈正相关;而与ER、PR表达及年龄无明显相关性;在179例浸润性导管癌中Cripto-1蛋白的表达与其组织学分级(r=0.194,P=0.009)呈正相关;E-CD表达在肿瘤细胞膜,而β-catenin除了表达在细胞膜外还表达在细胞质。Cripto-1的表达与E-CD呈明显负相关(r=-0.324,P=0.000),而与β-catenin在胞质中的表达呈明显正相关(r=0.412,P=0.000);Mann-Whitney检验结果显示Cripto-1蛋白在淋巴结阳性组的表达明显高于阴性组(Z=-3.465,P=0.001);在远处转移组的表达明显高于无远处转移组(Z=-3.899,P=0.000);Kaplan-Meier生存分析结果显示Cripto-1蛋白的表达程度与患者的生存率呈明显负相关(P<0.05);Cox-Regression证明Cripto-1蛋白的表达是乳腺癌独立的预后因素(HR=2.353)。结论:Cripto-1蛋白可能通过EMT促进乳腺癌的侵袭和转移,其表达与乳腺癌的侵袭、转移密切相关,是导致预后不良的重要因素之一,可作为乳腺癌的独立预后因子。Objective： To study the significance of Cripto-1, which plays an important role in EpitheliaI-Mesenchymal Transition （EMT）, and its prognosis in breast cancer. Methods： Immunohistochemistry for Cripto-1 was performed on 205 cases of breast cancer using LSAB method. The relationship between Cripto-1, E-cadherin （E-CD）, I8-catenin and various pathologic factors in breast cancer was analyzed. Additionally, the relationship between the Cripto-1 protein and reoccur- rence, metastasis, and survival time in patients was analyzed. Results： （1） Cripto-1 was mainly expressed in the plasma of tumor cells and the positive rate was 82.9% （170/205）. The expression of Cripto-1 was positively correlated with pathologic stage （r=0.418, P=0.000）, Her2/neu （r=0.223, P=0.001）, lymph node metastasis （r=0.293,P=-0.000）, extranodat extension （r=0.206, P=0.003）, and distant metastasis （r=0.174, P=0.012）. There was no correlation between Cripto-1 and ER, PR, or age. There was a positive correlation between the expression of Cripto-1 and histological grade （r=0.141, P=0.044） in 179 invasive ductal carcinomas. （2） E-CD was mainly expressed in the membrane of tumor cells. And 13-catenin was expressed in both the membrane and the plasma of tumor cells. The expression of Cripto-1 negatively correlated with E-CD （r=-0.324, P=-0.000） and positively correlated with 13-catenin which was expressed in the plasma of tumor cells （r=0.412, P=0.000）. （3） Mann-Whitney test showed that the level of expression in the lymph node-positive group was higher than that in lymph node-negative group （z =-3.465, P=-0.001）. The expression was higher in the metastatic group than in the non-metastatic group （z=-3.899, P=0.000）. Univariate Kaplan-Meier analyses revealed there was negative correlation between overexpression of Cripto-1 and survival （P〈0.05）. Cox-regression analysis indicated that the overexpression of Cripto-1 was an independent prognostic factor in breast cancer （HR, 2.353�

关 键 词：乳腺癌 Cripto-1蛋白 上皮间质转化 转移 预后 

分 类 号：R737.9[医药卫生—肿瘤]