Expression Of Claudin-7、E-cadherin And MMP-7 In Breast Infiltrating Ductal Carcinoma And Its Clinical Significance

Objective:Breast cancer is one of the most common malignant tumor in women around the world. In recent years, its incidence present a fast growth tendency in worldwide. In our country, breast infiltrating ductal carcinoma is the most common pathological types of breast cancer in women, which accounts for about 70%. Although the overall prognosis of breast cancer is well, there are still some patients died of postoperative metastasis. So it is necessary to further study the molecular biology mechanism in the occurrence,development, invasion and metastasis of breast cancer cells, to understand its key, and to find new diagnosis and treatment measure on this basis.A large number of studies suggest that the formation, invasion and metastasis of breast cancer is a stage-by-stage and step-by-step complex cascading reaction process and there are many factors involved. Most scholars support the four steps theory on invasion and metastasis of tumors,namely falling off, adhesion, degradation and movement. Tight junction protein Claudin-7 is a member of claudin family, its potential role is restricted to supply of cancer cell nutrition and growth factor.The tight junction protein Claudins can’t locate in the carcinoma cell membrane that is the key step of the tumor cell falling off and movement. E-cadherin(E-cad) plays an important role in promoting intercellular adhesion, maintaining cell polarity and stabilizing cellular structure. In tumor development process, MMP-7 is not only capable of degrading the extracellular matrix, but also can promote tumor angiogenesis. Therefore, Claudin-7, E-cad and MMP-7 may play an important role in the process of tumor formation, development, invasion and metastasis. This study detected Claudin-7, E-cad and MMP-7 expression in breast infiltrating ductal carcinoma, analyzed their correlated with tumor development, invasion and metastasis, and explored their interactionmechanism in the breast infiltrating ductal carcinoma, which may provide the theoretical basis for the prognosis of breast cancer.Methods: We collected 192 cases filed specimens paraffin block from breast ductal carcinoma tissue surgically removed from the department of pathology of Cang Zhou Central Hospital from October 2013 to October 2014.It included breast infiltrating ductal carcinoma(157cases), ductal carcinoma in situ(35cases). Another 30 cases normal breast tissue adjacent breast carcinoma were as control groups. All breast patients were not included the implementation of preoperative radiotherapy 、 chemotherapy and other treatment. All breast tissue paraffin blocks were cut into 7 pieces of 4μm-thick serial sections, in which one piece was used for conventional HE staining for pathological morphology, the remaining six pieces were used for immunohistochemical analysis of Claudin-7, E-cad and MMP-7 and negative control. Using immunohistochemical method to detect expression of Claudin-7, E-cad and MMP-7 in different breast tissues and to analyze the correlation between their expression in breast infiltrating ductal carcinoma and clinical pathological character. SPSS 13.0 statistical software was used for data analysis from thec 2test 、Fisher exact propability、Kruskal-Wallis H test、Wilcoxon rank sum test and Spearman rank correlation analysis. Test criterion for P <0.05 was statistically significant.Results:1 Claudin-7 and E-cad expression in adjacent breast cancer tissue, ductal carcinoma in situ, infiltrating ductal carcinoma is gradually decreased(P<0.05), statistically significant; MMP-7 expression in adjacent breast cancer tissue, ductal carcinoma in situ, infiltrating ductal carcinoma is gradually increased(P <0.05), statistically significant.2 Claudin-7, E-cad, MMP-7 expression in breast infiltrating ductal carcinoma had no relationship with age and menopause status, no statistically significant difference(P> 0.05); E-cad, MMP-7 expression in breast infiltrating ductal carcinoma had no relationship with tumor size, no statistically significant difference(P> 0.05), while Claudin-7 expression inbreast infiltrating ductal carcinoma had relationship with tumor size,statistically significant differences(P <0.05), tumor size increased when the Claudin-7 expression reduced; Claudin-7, E-cad, MMP 7-expression in breast infiltrating ductal carcinoma were associated with clinical stage, histological grade, lymph node metastasis and vascular invasion, there are statistically significant differences(P <0.05), Claudin-7 and E-cad pssitive expression rate decreased with increasing clinical stage, high histological grade incre, lymph node metastasis, and vascular invasion appeared, while the positive expression rate of MMP-7 increased.3 Pairwise correlation of Claudin-7 protein, E-cad protein, MMP-7protein was analysed by Spearman rank test, the results showed that the expression of Claudin-7 protein and E-cad protein was positively correlated(r= 0.261, P = 0.001), the expression of E-cad protein, MMP-7 protein and the Claudin-7 protein had no obvious correlation(r = 0.119, P = 0.138; r = 0.148,P = 0.064).Conclusion:1 Claudin-7, E-cad expression in adjacent breast tissue, ductal carcinoma in situ, infiltrating ductal carcinoma descended; MMP-7 expression in adjacent breast tissue, ductal carcinoma in situ, infiltrating breast Ductal carcinoma increased.2 Claudin-7, E-cad, MMP-7 expression in breast infiltrating ductal carcinoma had no relationship with age and menopause status; E-cad, MMP-7expression in breast infiltrating ductal carcinoma had no relationship with tumor size, while Claudin-7 expression in breast infiltrating ductal carcinoma had relationship with tumor size, tumor size increased when the Claudin-7expression reduced; Claudin-7, E-cad, MMP 7-expression in breast infiltrating ductal carcinoma were associated with clinical stage, histological grade,lymph node metastasis and vascular invasion, Claudin-7 and E-cad pssitive expression rate decreased with increasing clinical stage, high histological grade incre, lymph node metastasis, and vascular invasion appeared, while the positive expression rate of MMP-7 increased, suggesting that the deletion ofClaudin-7 and E-cad expression, increased expression of MMP-7 promote the progress of breast cancer, which may have relation with the poor prognosis of breast cancer patients.3 In breast infiltrating ductal carcinoma, the expression of Claudin-7 was positively correlated with the expression of E-cad, the expression of MMP-7was’ t correlated with the expression of Claudin-7 and E-cad. It suggested that Claudin-7 and E-cad may collaboratively promote the development of breast infiltrating ductal carcinoma, whereas MMP-7 may as an independent factor involved in the development of breast infiltrating ductal carcinoma.They may jointly participated in the process of development of different stages in breast infiltrating ductal carcinoma.