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Expression And Significance Of S100a4,annexina2 And Cathepsin B In The Breast Carcinoma

Posted on:2011-03-09Degree:MasterType:Thesis
Country:ChinaCandidate:X LiFull Text:PDF
GTID:2194330338458149Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Background:Breast carcinoma, one of the most common carcinomas in women, may be related to the genetic factors, the endocrine factors, the high-fat diet and so on, the peak age of the incidence of breast carcinoma is 45 to 50 years old. About 50 million people worldwide died from breast carcinoma each year.In the developed countries such as Western Europe and North America, the incidence of breast carcinoma is the first carcinoma in women. Breast carcinoma is less in China, but the incidence rate is increasing year by year, and it is in recent years that it has leapt to the top of women's carcinomas, or second place in our major cities.Calcium-binding protein S100A4 is a kind of calcium-binding proteins with the double helix structure of EF, and is made of 101 amino acids, which plays a role in the signal transduction inside and outside the cell, the cellur proliferation and differentiation, the secretion of extracellular matrix, the cell adhesion and the cell self-movement and other physiological processes.A large number of clinical studies have shown that the overexpression S100A4 gene was closely associated with the metastasis of prostate carcinoma, colon carcinoma and breast carcinoma. It can not only promote cell proliferation by combining with the tumor suppressor protein p53, but also play a role in the cell adhesion, the extracellular matrix renewal and the cell motility, thereby promoting tumor cell metastasis.AnnexinA2 is an important member of the annexins family, and is mainly located in the cell membrane, the cytoplasm and the extracellular. It can take part in a series of Ca2+ regulation of membrane-related biological activities, such as the fibrinolysis, the cell adhesion, the viral infection, the cytoskeletal activity, the membrane transport, the cell adhesion-mediated signal transduction, the cell proliferation, migration and differentiation and so on. It is found that the expression levels of annexinA2 changed in various tumor tissues:it was upregulated in the liver carcinoma, pancreas carcinoma, lung carcinoma, stomach carcinoma, pancreas carcinoma, colon carcinoma, and hematologic malignancies, while it was downregualted in prostate carcinoma.The abnormal expression of annexinA2 can make itself be a novel target of the judgment of the invasive ability and the gene therapy of carcinoma.Cathepsin B (CathepsinB, CB) is a major cysteine protease present in the lysosome, and plays a role in the proteolysis in physiological circumstances. Researches has showed that CB was a key kind of enzymes in the development of tumors.It is indicated in recent years that there were high expressions of CB in colon cancer, breast cancer, prostate cancer, ovarian cancer, liver cancer and other malignant tumors,which was closely related with the progression of the malignant tumors, and the degradation of extracellular matrix by which was considered as a critical step in invasion and metastasis.In addition, CB secreted by the tumor interstitial capillaries and fibroblasts could degrade the vascular basement membrane and the extracellular matrix, which was conducive to the migration of vascular endothelial cells, thereby contributing to the tumor angiogenesis.Objective:To investigate the expressions of S100A4, annexinA2, CB proteins in the breast invasive ductal carcinoma, breast normal tissues and benign breast lesions and their corelationship with invasion and metastasis. Method:The expressions of S100A4, annexinA2, CB proteins were detected by using the immunohistochemical SP method in 20 samples of breast normal tissues, in 20 samples of benign breast lesions and in 40 samples of the breast invasive ductal carcinoma.Results:1. The positive expression rate of S100A4 protein in 20 samples of normal breast tissues was 25.0%(5/20), the positive expression rate of S100A4 protein in 20 samples of breast benign lesions was 30.0%(6/20), the positive expression rate of S100A4 protein in 40 samples of the breast invasive ductal carcinoma was 67.5% (27/40). In breast invasive ductal carcinoma, the expression rate of S100A4 protein had relationships with lymph node metastasis (P<0.05) and did not have a relationship with the age and the tumor histological grade (P>0.05).2. The positive expression rate of annexinA2 protein in 20 samples of normal breast tissues was 10.0%(2/20), the positive expression rate of annexinA2 protein in 20 samples of breast benign lesions was 15.0%(3/20), the positive expression rate of annexinA2 protein in 40 samples of the breast invasive ductal carcinoma was 57.5% (23/40). In breast invasive ductal carcinoma, the expression rate of annexinA2 protein had relationships with lymph node metastasis and the tumor histological grade (P<0.05) and did not have a relationship with the age (P>0.05).3. The positive expression rate of CB protein in 20 samples of normal breast tissues was 15.0%(3/20), the positive expression rate of CB protein in 20 samples of breast benign lesions was 35.0%(7/20), the positive expression rate of CB protein in 40 samples of the breast invasive ductal carcinoma was 72.5%(29/40). In breast invasive ductal carcinoma, the expression rate of CB protein had relationships with lymph node metastasis and the tumor histological grade (P<0.05)and did not have a relationship with the age (P>0.05).4. In breast invasive ductal carcinoma,the correlation analysis demonstrated that the expression of S100A4 protein was positively correlated to that of annexinA2 protein (P<0.05) and was positively correlated to that of CB protein (P<0.05); the expression of annexinA2 protein was positively correlated to that of CB protein (P<0.001).Conclusion:1. S100A4,annexinA2 and CB protein in normal breast tissue and breast benign lesions is no expression or low expresseion, but in breast invasive ductal carcinoma is high expression.2. S100A4 protein involved in lymph node metastasis of breast invasive ductal carcinoma, AnnexinA2 protein and CB protein involved in invasion and lymph node metastasis of breast invasive ductal carcinoma.3. In breast invasive ductal carcinoma, the expression of S100A4 and annexinA2 and CB protein was positively correlated, it implies they have certain synergy to promote invasion and lymph node metastasis of breast invasive ductal carcinoma, participate in tumor invasion and metastasis.
Keywords/Search Tags:S100A4, annexinA2, CathepsinB, breast invasive ductal carcinoma, Immunohistochemistry
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