Study On The Expressions Of Matrix Metalloproteinases, Tissue Inhibitors Of Matrix Metalloproteinases And Its Value Of Prognosis In Breast Cancer

Objective: To observe the expressions of Matrix Metalloproteinases (MMPs) and their Tissue Inhibitors (TIMPs), Epidermal growth factor receptor (EGFR), Epidermal growth factor receptor-2 (C-erbB-2) in breast cancer, and explore their correlation with the invasive and metastasis of breast cancer. Bounding with 10 years follow-up data, to explore their relationship with the prognosis of breast cancer. The aim of these studies is to provide further rationale basis for MMPs and TIMPs family members in diagnostic study of prediction and monitoring of metastasis correlated with breast cancer and in remedial study of anti-breast cancer drugs. The other aim of these studies is to explore the application of Microarray immunohistochemical technique in the detection of the index correlated with breast cancer.Method: MMP-2, MMP-9, MMP-13, TIMP-1, TIMP-2, EGFR, C-erbB-2 were detected by Microarray and S-P immunohistochemical technique in 183 patients with breast cancer and 30 patients with benign breast disease.Results:1. The expression levels of MMP-2 (77.0%), MMP-9 (65.6%), MMP-13 (54.1%), TIMP-1 (61.2%), TIMP-2 (75.4%), EGFR (60.1%), C-erbB-2 (30.1%)in the breast cancer tissues were significantly higher than those of benign breast diseases (PO.01).2. In the MMPs, MMP-2 is correlated with the tumor size (P=0.010), and significantly correlated with clinical TNM stage, histological grade, and lymph node status. MMP-9 is correlated with the histological grade (P=0.012), and significantly correlated with tumor size, clinical TNM stage, and lymph node status (P <0.01). MMP-2 and MMP-9 had no correlation with age, pathological type, the status of ER and PR. MMP-13 is significantly correlated with clinical TNM stage, histological grade, and lymph node status. But had no correlation with age, the tumor size, pathological type, the status of ER and PR.3. In the TIMPs, TIMP-1 is correlated with the tumor size (^=0.049), and histological grade (P=0.014), and significantly correlated with clinical TNM stage and lymph node status. But had no correlation with age, pathological type, the status of ER and PR. TIMP-2 is significantly correlated with clinical TNM stage and lymph node status. But had no correlation with age, the tumor size, pathological type, the status of ER and PR. EGFR is significantly correlated with clinical TNM stage, histological grade, and lymph node status. But had no correlation with the tumor size, pathological type, the status of ER and PR.4. EGFR is correlated with lymph node status (P=0.016), and significantly correlated with clinical TNM stage (P <0.01). But had no correlation with age, the tumor size, pathological type, histological grade, the status of ER and PR.5. C-erbB-2 is correlated with the tumor size (P^.021), and significantly correlated with clinical TNM stage, histological grade, and lymph node status.But had no correlation with age, pathological type, the status of ER and PR.6. In breast cancer, the expression of MMP-2, MMP-9, and MMP-13 are inverse correlated with TIMP-1 and TIMP-2.7. The expression of C-erbB-2 is positive correlated with MMP-2.8. The survival rate of 5 years and 10 years in the group of MMP-2, MMP-9, and MMP-13 over-expression are lower than the group of low-expression.9. The survival rate of 5 years and 10 years in the group of TIMP-1 and TIMP-2 over-expression are higher than the group of low-expression.10. In the detection of the index correlated with breast cancer, Microarray imrnunohistochemical technique has no significantly difference with traditional immunohistochemical technique.Conclusion:1. In breast cancer tissues, the expression rate of MMP-2, MMP-9, MMP-13, TIMP-1 and TIMP-2 are all significantly higher than benign breast diseases. These indicate that MMPs and TIMPs play an important role in the carcinogenesis, development, invasive and metastasis of breast cancer.2. In breast cancer, the expression of MMP-2, MMP-9 and MMP-13 are significantly inverse correlate with TIMP-1 and TIMP-2. These indicate that there is a inverse feedback mechanism in human body. When the expression of MMPs is raised, the mechanism will up-regulate the expression of TIMPs so that to inhibit the degradation of the ECM and BM. these also indicate that the inhibitive relationship between MMPs and TIMPs are not always one-to-one.3. The survival rate of 5 years and 10 years in the group of MMP-2, MMP-9, and MMP-13 over-expression are lower than the group of low-expression. The survival rate of 5 years and 10 years in the group of TIMP-1 and TIMP-2 over-expression are higher than the group of low-expression. These indicate that MMP-2, MMP-9, MMP-13, TIMP-1 and TIMP-2 all could serve as markers for prognosis judgment of breast cancer patients.4. In the detection of the index correlated with breast cancer, Microarray immunohistochemical technique has no significantly difference with traditional immunohistochemical technique. These indicate that high-flux Microarray immunohistochemical technique could detect several indexes for many samples one time in the detection of the index correlated with breast cancer. It could save manpower, materials and financial resources. It is worth to spread and use.