| Breast cancer is one of the most common effects of contemporary women's health disorders, and its incidence is rising year by year in our country. In recent years,treatment of breast cancer is still surgery, supplemented by chemotherapy and endocrine therapy. However, these methods of breast cancer recurrence, metastasis, and advanced breast cancer, still can not achieve the desired effect. Because breast cancer is a heterogeneous disease, it is not yet applicable to all breast cancer treatment gold standard. Therefore, the establishment of specific immunotherapy of breast cancer,making it an important adjunctive therapy, or even the main treatment is the focus of current research tumor-associated antigens, the cancer/testis antigens (CTA) displayed thesepicific expression pattern.Now, tumor immunotherapy has become operative, the fourth mode of treatment of tumors after chemotherapy, and has targeted and less invasive and other characteristics,especially for some of the bad effects of breast cancer surgery after all, a good select.Among these, the identification of an appropriate target antigen, is the most critical step in breast cancer antigen-specific immunotherapy is the first step. Tumor antigens as targets for tumor immunotherapy, which is a prerequisite for high expression in tumor tissue, and low expression in normal tissues, or its expression is highly restricted in order to avoid that may occur during the treatment process itself autoimmune diseases.tumor-sepicific antigenic peptides which were presented to CD8+T lymphocytes by HLA-I class I molecules, and therefore inducing tumor sepicific killing.Cancer / testis antigens (cancer / testis antigen, CTA) is a tumor-associated antigen one of them, the expression in the testis and placenta, and in addition to the normal human tissues do not express, but more in the different tissue types species have a high expression in tumors, such as specific expression patterns, it has become an ideal target for cancer immunotherapy antigen. As one of CTA subfamily members,melanoma-associated antigen gene (Melanoma-associated antigen gene, MAGE) was isolated from melanoma cells, antigen gene is a big family. MAGE genes may encode tumor, its rejection antigen, the intracellular processing of the antigenic peptide, it and HLA-I molecules may bind to form a complex, may be from the cytotoxic T lymphocyte discernable, thereby inducing on the corresponding tumor cells caused by specific of killing.MAGE antigens expressed by different according to the mode, the MAGE family can be divided into two different types, the MAGE-I and MAGE-II class category.Among these MAGE-I antigen is a tumor-specific antigen,MAGE-II antigens in normal adult somatic cells are ubiquitously expressed, it is not within the scope of the CTA.MAGE-I antigens can be divided into three subgroups, the MAGE-A, MAGE-B and MAGE-C. Among these, MAGE-A contains 12 species, of MAGE-A 1 to MAGE-A 12.Now expression in breast cancer and the development of the role of MAGE-A 10 and MAGE-12 in breast malignancies in not more.Parameters from 75 primary breast cancer patients, mmunohistochemically detected the expressions.The study used immunohistochemistry to explore the MAGE-A 10 and MAGE-A 12 in breast cancer tissues and their corresponding non-malignant breast tissues from the protein expression levels, and with breast cancer the relationship between clinical parameters and prognosis. With the construction of MAGE-A10, MAGE-12 expression vector, gene transfection, RT PCR, Western-blot and immunoprecipitation and other research methods to explore the exogenous MAGE-A 10, MAGE-A 12-dependent breast cancer on estrogen cell proliferation and its mechanisms.Objective To test MAGE-A10 and MAGE-A12 in normal breast tissue,breast and non-malignant lesions and malignant lesions of the breast tissues, and to analyze their expression and breast cancer clinical indicators as well as the relationship between the prognosis.Methods Using RT-PCR and experimentally Immunohistochemistry were examined mRNA and protein MAGE-A 10 and MAGE-A 12 expression situation in 70 normal tissues,70 cases of benign breast tissues and 70 cases of malignant breast tissues,and then discuss them whether there is between the expression of breast cancer associated with clinical pathological parameters, including patient age, tumor extent, pathological type, histological grade, several clinical stage, axillary lymph node metastasis, vascular invasion, estrogen receptor ( Estrogenreceptor, ER), progesterone receptor(Progestrogen receptor, PR), and HER-2. Through patient follow-up, expression and association studies of breast cancer prognosis between MAGE-A10 and MAGE-A 12 proteins.Results 1 MAGE-A 10 and MAGE-A 12 in the normal testis performancePositive result of the selection of normal testicular tissue as MAGE-A 10 and MAGE-A 12 performance control. In normal testis, MAGE-A 10 and MAGE-A 12 are mainly in primary spermatocytes (primary spermatocyte, PSC) and spermatogonia(spermatid, ST) in the performance of its positive results matter most in the cytoplasm,small section located in the nucleus.2 MAGE-A 10 and MAGE-A 12 non-malignant breast tissue and malignant breast tissue performanceResults Immunohistochemical staining showed that, MAGE-A 10 immunohistochemical staining positive results in the matter of malignant breast tissues mainly located in the cytoplasm, a small part in the nucleus, 70 cases of normal breast lesions found no expression of MAGE-A 10 proteins, 70 cases of malignant breast lesions has 53 cases of MAGE-A 10 protein expression was positive, the percentage of positive results was 75.7%, significantly higher than normal breast lesions performance(P <0.05). The above results show that the tumor antigen MAGE-A10 specific.Results Immunohistochemical staining showed that, MAGE-A 12 in malignant breast tissues by immunohistochemical staining positive results substance is mainly located in the cytoplasm, a small part in the nucleus. 70 cases of normal breast lesions found no expression of MAGE-A12 protein, 70 cases of malignant breast lesions has 39 cases of MAGE-A 12 protein expression was positive, the percentage of positive results was 55.7%, significantly higher than normal breast lesions performance ( P <0.05). The above results show that the tumor antigen MAGE-A12 specific.3 Correlation between MAGE-A10 and MAGE--A12 protein expression and clinical and pathological signs of breast cancerStatistical results show, MAGE-A 10 protein expression in breast cancer and the patient's age (?2 = 1.006, P = 0.632), pathological type (?2 = 2.287, P = 0.151),histological grade (?2 = 0.595, P =0.684), clinical stage (?2 = 1.404, P = 0.496), tumor size (x2 = 0.617, P =0.702), lymph node metastasis (?2 = 0.042, P = 0.720), ER (?2 =1.747, P = 0.194) and PR (?2 0.507, P = 0.506) are not relevant.MAGE-A12 protein expression in breast cancer and the patient's age (?2 =0.502, P=0.753), pathological type (?2 = 0.029, P = 0.785), histological grade (?2 ? 0.699, P =0.701), clinical stage (?2 = 0.586, P = 0.605), tumor size (?2 = 2.400, P = 0.289), lymph node metastasis (?2 = 2.296, P = 0.203), PR expression (?2 = 0.173, P = 0.706) are not correlated (P > 0.05),but the expression of ER showed positive correlation. 37 cases of breast cancer patients with ER expression in the expression of MAGE-A12 protein 26 cases were positive (69.7%), 38 cases of ER expression in breast cancer patients with non-positive in 15 cases MAGE-A 12 proteins that were positive (36.2 %), with statistical significance (?2 = 8.381, P = 0.006) between both.4 Correlation between MAGE-A10 and MAGE-A12 protein expression of HER-2 expressionResults Immunohistochemical staining showed that, HER-2 positive immunohistochemical staining substances in breast cancer in the majority located in the cell membrane. Statistical analysis of the results showed that 70 cases of breast cancer patients, 8 cases of HER-2 expressed as (-) (11.4%), 28 cases of HER-2 expression is (+)(40%), 19 cases of HER-2 expression (++) (27.1%), 15 cases of HER-2 expression (+++)(21%).Statistical analysis showed that the expression of MAGE-A 10 and HER-2 expression had no correlation (?2 = 1.583, P = 0.643). HER-2 positive breast cancer patients showed the MAGE-A12 protein expression was significantly higher than the performance of HER-2 negative breast cancer patients (?2 = 14.032, P = 0.004).5 Correlation between MAGE-A10 and MAGE-A12 expressions and the survival of breast cancer patientsStatistical results show, MACE-A 10 breast cancer patients showed a positive survival and MAGE-A 10 showed negative breast cancer patients compared to no significant differences between them (P ? 0.821). MAGE-A 12 breast cancer patients showed a positive survival and MAGE-A12 exhibited negative breast cancer patients compared to significantly lower (P = 0.030). Tips, MAGE-A 12 protein expression,there may be an important identification of breast cancer patients with poor prognosis.Conclusion 1 normal breast lesions did not express MAGE-A 10 and MAGE-A12 protein. MAGE-A 10 and MAGE-A 12 expression in breast cancer tissues were 75.7%and 55.7%, respectively. Showed that the tumor antigen MAGE-A 10 and MAGE-A 12 specific.2 MAGE-A10 protein expression in breast cancer and the patient's age,pathological type, histological grade, clinical stage, tumor extent, lymph node metastasis, ER and PR status were not associated with the performance.3 MAGE-A 12 protein expression in breast cancer and the patient's age,pathological type, histological grade, clinical stage, tumor extent, lymph node metastasis, PR expression are not associated, but with the expression of ER was positively correlated. Breast cancer patients with positive expression of the MAGE-A 12 protein exhibited significantly higher ER ER-negative breast cancer showed.4 MAGE-A 10 protein expression of HER-2 expression is not associated.MAGE-A12 protein expression was positively correlated with HER-2 performance. The expression of the MAGE-A12 breast cancer protein HER-2 showed a significantly higher expression HER-2 negative breast cancer patients. This suggests that,MAGE-A12 protein expression may be associated with poor prognosis in breast cancer is associated.5 MAGE-A10 protein expression was positive breast cancer patient survival and expression of MAGE-A 10-negative breast cancer patients compared with no significant difference. MAGE-A 12 protein expression in breast cancer patients with positive survival and expression of MAGE-A 12 breast cancer patients with negative comparison,is significantly reduced. This suggests that, MAGE-A 12 protein expression may be an important identification of breast cancer patients with poor prognosis. |
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