中文摘要：

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蛋白在淋巴结阳生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.

英文摘要：

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?