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

Abstract

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),β-catenin and various pathologic factors in breast cancer was analyzed.Additionally,the relationship between the Cripto-1 protein and reoccurrence, 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),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 cells.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 positively correlated with β-catenin which was expressed in the plasma of tumor cells (t=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 (P0.05).Cox-regression analysis indicated that the overexpression of Cripto-1 was an inde- pendent prognostic factor in breast cancer (HR,2.353).Conclusion: Cripto-1 may,through EMT,promote invasion and metastasis. Moreover,overexpression of Cripto-1 may prove to be of clinical value in breast cancer as an independent prognostic factor for improving the estimation of prognosis and guiding therapeutic decisions.