Expressions Of ADAM-17 In Human Breast Invasival Cancer And Its Clinical Significance

Objective: To study the significance of ADAM-17 protein expressions in invasive breast carcinoma and their relationship with clinical pathological results, to investigate the feasibility to become the new index of the targeted therapy in breast cancer.Method: We investigated the protein expression of ADAM-17 in 108 cases of breast carcinomas tissue collected from the inpatients who received surgical operation in the hosipital of Hebei United University for breast cancer from Octorber 2008 to Janeary 2010. Following about 20g surgical tumour resection tissue, and snap-stored at -80℃by Western blot, other tissue samples fixed in 10% neutralised formalin and paraffin-embedded. Serial sections were cut at 6μm for immunohistochemistry. The expressions of ADAM-17 protein were detected in 108 invasive breast carcinoma samples by Western blot and SABC immunohistochemical (IHC) analysis, and to study correlation with histological type,histological grade,the clinical stage,and lymph node metastasis. (2) We investigated the protein expression of ADAM-17 in 108 cases of breast invasival carcinomas, Histological type: 82 cases of Non-special type of invasive ductal carcinoma,13 cases of Non-specific type invasive lobular carcinoma,13 cases of Special type of invasive carcinoma ; Histological grad(e82 cases):32 cases ofⅠgrade,36 cases ofⅡgrade,14 cases ofⅢgrade;Clinical stage:36 cases ofⅠstage,49 cases ofⅡstage,23 cases ofⅢstage;56 cases of No Lymph-node metastasis, 52 cases of No Lymph-node metastasis. Data obtained from the results of the application package SPSSl5.0 statistical analysis to P<0.05 for the difference has statistical significance. Results: (1) Using immunohistochemistal staing methods:The positive staining of ADAM-17 protein was seen in the cytoplasm of breast invasive ductal carcinoma (IDC) cells.Histological type in 108 cases of breast carcinomas tissue: The positive expression rate of ADAM-17 was 69.5 % (57/82), 84.6 % (11/13) and 61.5 % (8/13) in Non-special type of invasive ductal carcinoma tumor tissue,Non-specific type invasive lobular carcinoma and Special type of invasive carcinoma, respectively. The positive expression rate of ADAM-17 was not elevated significantly in tumor tissue compared to Non-specific type invasive lobular carcinoma the same as in Special type of invasive carcinoma compared to Non-special type of invasive ductal carcinoma (P=0.411). Histological grade (82 cases): The positive expression rate of ADAM-17 was 53.1%(17/32), 75.0%(27/36) and 92.9%(13/14) in cases ofⅠgrade,cases ofⅡgrade,cases ofⅢgrade, respectively. The positive expression rate of ADAM-17 was elevated significantly in tumor tissue compared to cases ofⅢgrade the same as inⅠgrade compared to cases ofⅡgrade (P=0.001). Clinical stage: The positive expression rate of ADAM-17 was 55.6%(20/36), 69.4%(34/49) and 95.7% (22/23) in cases ofⅠstage,cases ofⅡstage,cases ofⅢstage, respectively. The positive expression rate of ADAM-17 was elevated significantly in tumor tissue compared to cases ofⅢstage the same asⅠstage compared to cases ofⅡstage (=0.004). The positive expression rate of ADAM-17 was different significantly in 56 cases of No Lymph-node metastasis compared to 52 cases of No Lymph-node metastasis (P=0.000).(2) Using Western Blott technique: Western blotting found that ADAM-17 protein has different expression in 108 cases of breast carcinomas tissue. The expresive situation of ADAM-17 protein: The expression of Histological type in 108 cases of breast invasive carcinomas tissue, 82 cases of Non-special type of invasive ductal carcinoma,13 cases of Non-specific type invasive lobular carcinoma,13 cases of Special type of invasive carcinoma, The ratio of the average OD value of the ADAM-17 expression detected by Western blot technique were 0.383±0.026,0.382±0.021 and 0.387±0.025. the expression rate of ADAM-17 protein among them had no significant difference(P=0.396).The expression of Histological grade in 82 cases of breast invasive carcinomas tissue, 32 cases ofⅠgrade,36 cases ofⅡgrade,14 cases ofⅢgrade, The ratio of the average OD value of the ADAM-17 expression detected by Western blot technique were 0.382±0.016,0.384±0.019 and 0.413±0.029, the expression rate of ADAM-17 protein among them had significant difference(P=0.002),and it is significantly up-regulated in breast cancer. The expression of Clinical stage in 108 cases of breast invasive carcinomas tissue, 36 cases ofⅠstage,49 cases ofⅡstage,23 cases ofⅢstage, The ratio of the average OD value of the ADAM-17 expression detected by Western blot technique were 0.372±0.015,0.385±0.016 and 0.398±0.029, the expression rate of ADAM-17 protein among them had significant difference(P=0.005),and it is significantly up-regulated in breast cancer. There were 56 cases of No Lymph-node metastasis in 108 cases of breast carcinomas tissue, The ratio of the average OD value of the ADAM-17 expression detected by Western blot technique were 0.377±0.016, there were 52 cases of Lymph-node metastasis, The ratio of the average OD value of the ADAM-17 expression detected by Western blot technique were 0.393±0.029, the expression rate of ADAM-17 protein between them had significant difference(P=0.000).Conclusion:1. There has highly expression of ADAM-17 protein in invasive breast carcinoma.2. The expression of ADAM-17 protein in invasive breast carcinoma was correlated with histological grade, the clinical stage of the carcinoma, and lymph node metastasis,but without histological type.3. The expression of ADAM-17 protein in invasive breast carcinoma is significantly up-regulated with histological grade and the clinical stage up-regulating.4. High levels of ADAM-17 can be used as a new indicator to diagnose breast carcinomas in clinical, and a new target gene to treat breast cancer.