Expression And Clinical Significance Of Paxillin And Caspase-3 In Invasive Ductal Carcinoma Of Breast

Background and objectivesBreast cancer is a malignant disease which seriously influences female health. The incidence of breast cancer accounts for the first position of female malignant tumors globally. Infiltrating ductal carcinoma of breast cancer is one of the largest group of alien tumor, degree of malignancy is extremely high. The study of breast cancer happening mechanism and metastasis characteristics has become the hot spot in the study of tumor. Paxillin is a phosphoric acid protein on the cytoskeleton, which can bind to vinculin and adjust the cells to move and disseminated and other functions. Paxillin plays an important role in the signal transduction pathways which is mediated by integrin. Paxillin also plays a key role In breast cancer cell adhesion, increase, migration and the malignant transformation process, it may be the evaluation index of the prognosis of breast cancer. Caspase-3 is one of the apoptosis executives in caspase, the signaling pathway mediated by caspase-3 plays an unique role in the process of cell apoptosis. the abnormal expression of caspase-3 effect on the process of cell apoptosis may closely related with the occurrence of malignant tumor development. The lower expression of caspase-3 may play an important role in the development of the tumor. At the same time, paxillin plays a role in the singaling pathways as the cracking substrates of caspase-3, which indicated the inner linker between paxillin and caspase-3 in the development of the tumor. In this study, we investigate the expression of paxillin and caspase-3 and their relationship with the clinicopathologic character and their significance in breast cancer, so as to provide a potential theory for the early diagnosis and anti-apoptosis therapy in breast cancer.1 Materials and MethodsMaterials:A total of 60 cases of surgical resection of primary breast invasive ductal cancinoma specimens (in the cancer center and avoid central necrosis of tissue) were enrolled from the department of the breast surgery of the first affiliated hospital of Zhengzhou University from January 2006 to December 2007, another 25 normal breast tissue confirmed by pathology were randomly selected from the 60 cases which distance to lesion about 5cm as the control group. All specimens were female patients, with age ranging from 25-71(median age was 45). The patients were staged clinically according to the international Tumor-Node-Metastasis system (UICC), stageⅠ(19 cases),stageⅡ(26 cases), stageⅢ(15 cases). Histological grading and staging were classified according to World Health Organization (WHO) standards,, gradeⅠlevel (16 cases), gradeⅡlevel (20 cases), gradeⅢlevel (24 cases). Axillary lymph node metastasis appeared 41 cases, without lymph node metastasis 19 cases. The expression of ER, PR and the state of her-2 according to the immunohistochemical results of the pathology department of the first affiliated hospital of zhengzhou university. All patients were not receiving preoperative radiotherapy, chemotherapy or endocrine therapy, All patients were executed radical or modified radical mastectomy, All lesions were invasive ductal carcinoma confirmed by postoperative routine pathology. All sample tissues were fixed by 10% formalin and embedded by paraffin for experiment of immunohistochemistry.1.2 Main reagent, paxillin mouse monoclonal antibody, (NeoMarkers, USA), caspase-3 rabbit polyclonal antibody (boshide goldbridge biotechnology company), S-P agent box and DAB agent(zhongshang goldbridge biotechnology company).1.3 Immuohistochemistry paxillin and caspase-3 were performed on cases using paxillin antibody at 1:100, caspase-3 antibody at 1:400, and PBS was used as negative control.1.4 Statistical analysis SPSS 17.0 software was used for statistical analysis. Chi-square test was used to analyze the date.The correlation of paxillin and caspase-3 was analyzed with Spearman rank correlation. Results were considerable statistically significant at the level of a=0.05.2 results2.1 the expression of paxillin in IDC and normal tissueThe positive rates of paxillin in IDC group was 65.00%(39/60), while the data was 40.00%(10/25) in normal mammary tissue group. Compared with normal mammary specimen group, the expression of paxillin in the IDC was obviously high-regulated. And there was statistically difference (P<0.05). The expression of paxillin in the IDC group was closely correlated with the histological grade, the lymph node metastasis and the her-2 state (P<0.05), but not correlated with the age,menses, TNM stage, ER and PR.2.2 the expression of caspase-3 in IDC and normal tissueThe positive rates of caspase-3 in IDC group was 45.00%(27/60), while the data was 72.00%(18/25) in normal mammary tissue group. The expression level of caspase-3 in the IDC was obviously down-regulated, when compared with normal mammary specimen group. And there was statistically difference (P<0.05). The expression of caspase-3 in the IDC group was closely correlated with the histological grade and the lymph node metastasis (P<0.05), but not correlated with the age,menses, TNM stage, ER and PR. 2.3 the correlations among paxillin and caspase-3 There is a negative correlation between paxillin and caspase-3 in invasive ductal carcinoma (r=-0.320、p=0.013)3 Conclusions3.1 The expression of paxillin was higher in invasive ductal carcinoma than the normal tissue, The difference between IDC and normal mucosa tissue is statistically significant (P<0.05), and the expression of paxillin in the IDC group was closely correlated with the histological grade, the lymph node metastasis and the her-2 state (P<0.05), but not correlated with the age,menses, TNM stage, ER and PR. paxillin might be new markers in prediction for IDC, and new therapeutic targets for IDC which was her-2 negative.3.2 The expression of caspase-3 was lower in invasive ductal carcinoma than the normal tissue, The difference between IDC and normal mucosa tissue is statistically significant (P<0.05), and the expression of caspase-3 in the IDC group was closely correlated with the histological grade and the lymph node metastasis (P<0.05), but not correlated with the age,menses, TNM stage, ER and PR..caspase-3 might plays a key role in early diagnosis of invasive ductal carcinoma.