Cripto-1 蛋白在乳腺癌中的表达和预后意义*

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。 

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

Objective: To study the significance of Cripto-1, which plays an important role in Epithelial-Mesenchymal Transition (EMT), and its prognosis in breast cancer. Methods:Immunohistochemistry for Cripto- 1 was performed on205 cases of breast cancer using LSAB method. The relationship between Cripto- 1, E-cadherin (E-CD), β-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 ), Her 2/neu ( r=0.223 , P=0.001 ), lymph node metastasis (r=0.293 ,P=0.000 ), extranodal 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 cel ls. And β-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 posi tively correlated wi th β-catenin which was expressed in the plasma of tumor cel ls (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 overexpres-sion 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 ). Conclusion:Cripto-1 may, through EMT, promote invasion and me-tastasis. Moreover, overexpression of Cripto-1 may prove to be of clinical value in breast cancer as an independent prog-nostic factor for improving the estimation of prognosis and guiding therapeutic decisions.