The Expression Of Cripto-1 And Its Prognosis Significance In Breast Cancer

ObjectiveBreast cancer is a common cancer of women, which is a group of malignant epithelial tumors, characterized by tumor-infiltrating adjacent tissue, and an obvious tendency of distant metastasis. Our research was to study the significance of Cripto-1 which play an important role in Epithelial-Mesenchymal Transition(EMT) and its prognosis in breast cancer.MethodsImmunohistochemical study for Cripto-1, E-CD and P-catenin were performed on 205 cases of breast cancer using LSAB methods. The relationship between Cripto-1, E-CD, P-catenin and various pathologic parameters (estrogen and progesterone receptor status, Her2/neu status,histologic grade, pathologic stage and lymph node metastasis etc.) in breast cancer was analyzed. And also analyzed the univariate Kaplan-Meier survival and Cox-regression survival.Results1. Cripto-1 was mainly expressed in the plasma of tumor cells. Upregulated Cripto-1 was found in 82.9%(170/205)cases. The expression of Cripto-1 was positively correlated with pathologic stage(r=0.357, P=0.000), histological grade(r=0.141, P=0.044), 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=0.273, P=0.000).2. E-CD was expressed in the membrane of the breast cell, downregulated of E-CD was found in 54.1%(111/205) cases. The expression of E-CD was negatively correlated with pathologic stage(r=-0.165, P=0.018), histological grade(r=-0.151, P=0.031), lymph node metastasis(r=-0.154, P=0.027), extranodal extension(r=-0.200, P=0.004).3. P-catenin was expressed in the cytoplasma and nuclear in EMT and was found in 67.3% (138/205) cases. The expression ofβ-catenin was positively correlated with pathologic stage(r=0.193, P=0.006), lymph node metastasis(r=0.153,P=0.028).4. The expression of Cripto-1 was negatively correlated with E-CD(r=-0.324, P=0.000)and positively correlated with P-catenin(r=0.412, P=0.000). Combined evaluation Cripto-1/E-CD and Cripto-1/β-catenin, Cripto-1+/E-CD-was strongly associated with pathologic stage(χ2=14.502,P=0.002), lymph node metastasis(χ2=12.858, P=0.005), extranodal extension(χ2=9.275, P=0.002),distant metastasis((χ2=4.654, P=0.045), and Cripto-1+/β-catenin+ was strongly associated with pathologic stage(χ2=14.334, P=0.002), lymph node metastasis(χ2=8.734, P=0.033), distant metastasis(χ2=5.400,P=0.020).5. Univariate Kaplan-Meier survival analysis reveals that patient with Cripto-1+, E-CD-orβ-catenin which localized in the cytoplasm showed lower survival rates than those with Cripto-1 -, E-CD+ orβ-catenin which localized in the membrane(P<0.05). When combined,evaluation of Cripto-1 and E-CD, Cripto-1 andβ-catenin, Cripto-1+/E-CD - and Cripto-1+/β-catenin+ indicated the worst 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).Conclusion1. Upregulation of Cripto-1, downregulation of E-CD and relocalization of P-catenin may play important roles in the invasion and metastasis of breast cancer.2. overexpression of Cripto-1 was a significantly factor for prognosis.3. Cripto-1 protein was a new target for the breast cancer treatment.