| Breast cancer is one of the most common malignant tumor which influences women's health and even life-threatening, and its incidence accounts for the first position of female malignant tumors globally, and has the trend of further increasing in recent years. Also, the incidence of this disease is increasing gradually in China these years. The metastasis of vital organs is the main cause of death. The most common type of breast cancer is the invasive ductal carcinoma, and the mechanism of the development and progress of breast cancer is still the focus of current research. Caspase-3 is considered to be a central protease in the execution of apoptosis. The expression of Caspase-3 not only reflects apoptosis level but also alludes to the exist of apoptotic start-up factor. Osteopontin (OPN) is a secreted, integrin-binding matrix protein that is produced by a number of tissues and cells. It can promote physiological processes of cell chemotaxis, adhesion, migration, calcium metabolism and vascular remodeling. It is indicated that the increased expression of OPN is closely correlated with the formation and progression of most malignant tumor. Ezrin plays a key role in cell surface structure adhesion, migration, organization and has certain relation to apoptosis. Caspase-3, OPN and Ezrin all have some impact on tumor progression and development of metastasis. However, there are fewer studies on the correlation between expression of these three factors and IDC of breast. This study will provide some grounds for the effectiveness of the three in breast invasive ductal carcinoma.ObjectiveTo investigate the expression of Caspase-3, OPN, Ezrin and their relationship with the clinicopathologic character and their significance in invasive ductal cancinoma of breast.Materials and MethodsMaterials:The samples were from 71 cases of surgical resection of primary breast invasive ductal cancinoma specimens (in the cancer center and avoid central necrosis of tissue) in the department of pathology of the First Affiliated Hospital of Zhengzhou University from January 2003 to December 2004. Another 33 normal breast tissue confirmed by pathology were randomly selected from the 71 cases which distance to lesion about 5cm as the control group. All specimens were female patients, aged 22 to 72 (median age was 45), who were not receiving preoperative radiotherapy, chemotherapy or endocrine therapy. The patients were staged clinically according to the international Tumor-Node-Metastasis system (UICC), stageⅠandⅡ(45 cases), stageⅢandⅣ(26 cases); Axillary lymph node metastasis (50 cases), no axillary lymph node metastasis (21 cases); Histological grading and staging were classified according to World Health Organization (WHO) standards, gradeⅠ(15 cases), gradeⅡ(24 cases), gradeⅢ(32 cases).50 cases were followed up for 5 years or more, all of which had complete following-up information, but the rest failed to be followed up. Among these 50 patients,27 of them occured metastasis or recurrence. The survival rate:≥5 years,32cases;<5 years,18 cases. All patients were executed radical or modified radical mastectomy according to the results of intraoperative rapid frozen. 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.Methods:The expression of Caspase-3, OPN, Ezrin were detected by immuno-histochemistry (S-P) in 71 IDC tissues and 33 normal mammary specimens. To analyse the corelation between the expression of Caspase-3, OPN, Ezrin and clinical pathological characteristics of IDC of breast. The statistical analysis was executed by SPSS 18.0 software. The difference between groups and relationship between the three indicators and pathological parameters of breast cancer were analyzed using chi-square test, significance levelα=0.05. The correlation between the three indicators was analyzed by calculating contingency coefficients with pearson method.ResultsThe positive rates of Caspase-3 was 43.66% (31/71) in IDC group, while the data was 75.76% (25/33) in normal mammary tissue group. Compared with normal mammary specimen group, the expression of Caspase-3 in the IDC group was obviously down-regulated. The difference was statistically different (P<0.05). The expression of Caspase-3 in the IDC group was closely correlated with the lymph node metastasis, recurrence and 5-year survival rates.The positive rates of OPN were 74.65% (53/71) and 33.33% (11/33) in IDC and normal mammary tissues. The expression of OPN in the IDC group was significantly up-regulated compared with normal mammary specimen group. The expression of OPN in the IDC group was closely correlated with the lymph node metastasis, recurrence and 5-year survival rates of IDC (P<0.05), suggesting that up-regulation of OPN may be associated with breast cancer metastasis and recurrence.The positive rate of Ezrin in IDC group (64.79%) was more increased than that in normal mammary specimen group(39.39%). There was significant difference between two groups (P<0.05). Elevated expression of Ezrin is associated with advancing histological grade, clinical stage and lymph node metastasis of breast cancer. Also, the expression of Ezrin in IDC group was closely correlated with recurrence and 5-year survival rates (P<0.05), and is helpful in assessing the malignant degree, invasion and metastasis of IDC.Positive expression of Caspase-3 was negatively related to those of OPN and Ezrin in invasive ductal carcinoma (r=-0.258,-0.313, P=0.023,0.004), while positive expression of OPN was positively related to that of Ezrin (r= 0.29, P=0.008).ConclusionsThe expression of Caspase-3 in the IDC group was obviously down-regulated. The expression of OPN and Ezrin in the IDC group were significantly up-regulated compared with normal mammary specimen group, so the abnormal expression of Caspase-3, OPN and Ezrin play independent and collaborative roles in the occurrence and development of IDC. |
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