The Expression And Clinical Significance Of Apaf-1,Caspase-9,Bax,Bcl-2 And P53 In Basal-like Breast Carcinoma

Breast cancer that threaten the health and life of women seriously is one of the most common female malignant tumor, There are about one million new cases each year around the word. At present, the breast cancer were divided into 5 subtypes:luminal A subtype,luminal B subtype,normal breast-like subtype,HER-2 over-expressing subtype,basal-like subtype, They have the independent biological behavior and clinical prognosis. Basal-like breast carcinoma(BLBC) accounted for about all of the 15%-25% of breast cancer, the clinical manifestations, histopathological and immunohistochemical pheno-type were quite characteristic, local recurrence and distant metastasis occurred easily after operation, no sensitive to mature endocrine therapy, there was currently no effective targeted therapy method, BLBC caused widespread concern as a new understanding of the special breast cancer subtypes.Cell apoptosis was a process that an organism with physiological or pathological conditions started their own internal procedures through a variety of ways of signal transfer. This experiment mainly introduced the occurrence and development of basal-like breast cancer from the mitochondrial pathway of apoptosis, the associated protein have Apaf-1, Caspase-9, Bax, Bcl-2, p53.The homolog of Apaf-1(apoptotic protease activating factor1) in nematode is Ced-4, it played an important role in the mitochondrial apoptosis pathway in the brain of stroke, the mouse neural cells were excessive and their brain were malformation after gene knockout. Apaf-l can activate Caspase-3, and the activation process need to participate in Cyt-C and Caspase-9. After Apaf-1/Cyt-C complex combined with ATP/d ATP, Apaf-1 combined with Caspase-9 via its CARD domain to form apoptotic body, and the body activated Caspase-3 and start the Caspase cascaded reaction.Caspase is a family of cysteine proteases. In the mitochondrial pathway of apoptosis, Caspase-9 was located in the upper reaches of cascade reaction, and one of the most important factors of origin. It activated itself in other proteins involved in and activated other Caspase factors downstream, and then caused cascaded amplification effect, resulting in cell apoptosis.Bcl-2 gene was also called apoptosis suppressor gene, it is an oncogene separated off from B cell lymphoma and associated with programmed cell death. The study found that the Bcl-2 gene and its protein can inhibit cell apoptosis in various tissues.Bax gene is one of the Bcl-2 gene family, it can promote apoptosis, and it acted on mitochondria with Bcl-2 to regulate cell apoptosis.The p53 is one of the tumor suppressor genes that studied the most deeply and widely, the p53 protein is a nuclear protein and it can cause cell cycle arrest, induce apoptosis and promote differentiation, but the mutant p53 losted the suppressor effect, it can induce cell growth, arrest cell apoptosis and differentiation and DNA repair, and then became an important factor in the process of tumor development.This study was to detect the expression of Apaf-1,Caspase-9,Bcl-2,Bax, p53 in basal-like breast carcinoma and to investigate the relationship between basal-like breast carcinoma and cell apoptosis of mitochondrial pathway, it was a preliminary study on the occurrence and development mechanism of basal-like breast carcinoma, and it would provide a theoretical basis for clinical treatment of patients with basal-like breast carcinoma.Objective:By detecting the expression of Apaf-1,Caspase-9,Bax,Bcl-2 and p53 in basal like breast carcinoma to investigate the relationship between basal-like breast cancer and cell apoptosis of mitochondrial pathway, and it was a preliminary study on the occurrence and development mechanism of basal-like breast cancer, and it would provide a theoretical basis for clinical treatment of patients with basal-like breast cancer.Methods:Select 43 cases of basal-like breast cancer(BLBC), 57 cases of non-basal-like breast cancer(non-BLBC), 60 cases of normal breast tissue(From the edge of tumor 5cm),to use immunohistochemical method to detect the expression of Apaf-1,Caspase-9,Bax,Bcl-2,p53 protein in BLBC,non-BLBC and normal breast tissue,and to analyse the correlationship between Apaf-1,Caspase-9,Bax,Bcl-2,p53 and age,tumor size,lymph node metastasis,TNM staging; applicating SPSS17.0 statistical software, count data using χ2 test, correlation analysis using Spearman correlation, P<0.05 had significant difference.Results:1. The positive expression rate of Apaf-1 in BLBC was 23.26%(10/43) and 54.39%(31/57) in non-BLBC and 75.00%(45/60) in normal breast tissue, comparing with each other, the difference had statistical significance.2. The positive expression rate of Caspase-9 in BLBC was 27.91%(12/43) and 54.39%(31/57) in non-BLBC and 85.00%(51/60) in normal breast tissue, comparing with each other, the difference had statistical significance.3. The positive expression rate of Bax in BLBC was 20.93%(9/43) and 45.61%(26/57) in non-BLBC and 76.67%(46/60) in normal breast tissue, comparing with each other, the difference had statistical significance.4. The positive expression rate of Bcl-2 in BLBC was 69.77%(30/43) and 43.86%(25/57) in non-BLBC and 21.67%(13/60) in normal breast tissue, comparing with each other, the difference had statistical significance.5. The positive expression rate of Apaf-1 in BLBC was 79.07%(34/43) and 52.63%(30/57) in non-BLBC and 5.00%(5/60) in normal breast tissue, comparing with each other, the difference had statistical significance.Conclusions:The expression of Apaf-1 in basal like breast carcinoma(BLBC) was significantly lower than that in the non-basal like breast carcinoma(non-BLBC) and the normal breast tissue, and the expressions of Apaf-1,Caspase-9,Bax have positive correlation. The expression of Bcl-2,p53 in BLBC was higher than that in non-BLBC and normal breast tissue, and they have positive correlation. The expression of Apaf-1 in BLBC was independent with patient’s age, but it was related with tumor size,lymph node metastasis,TNM staging. The expression of Caspase-9,bcl-2,bax,p53 in BLBC was independent with patient’s age and tumor size, but it was related with lymph node metastasis and TNM staging(p<0.05), Apaf-1, Caspase-9, bcl-2,bax,p53 may be closely related to the occurrence and development of BLBC.