[Expression and clinical significance of MMP-2, MMP-9,TIMP-1, and TIMP-2 in breast carcinoma].

Background & Objective: Expression imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play pivotal roles in tumor invasion and metastasis. But little is known about the correlation between their expression and breast cancer prognosis. The aim of this study was to investigate the expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 in breast carcinomas and to seek their relationship with breast cancer invasion, metastasis, and prognosis.

Methods: Sixty-six patients of breast cancer with clinical features and survival data were enrolled. The mRNA expression of TIMP-2, MMP-2 were determined using in situ hybridization. The protein expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined using immunohistochemistry. The results were analyzed using chi-square test, Kaplan-Meier method, and Cox multivariate regression analysis.

Results: The positive expression rates of TIMP-2 mRNA, MMP-2 mRNA and MMP-2, MMP-9, TIMP-1, and TIMP-2 protein were 66.7% (44/66), 65.2% (43/66) and 71.2% (47/66), 68.2% (45/66), 40.9% (27/66), 69.7% (46/66), respectively. The expression of MMP-2 protein had positive correlation with those of MMP-2 mRNA and MMP-9 protein(P< 0.01). The expression of TIMP-2 mRNA had positive correlation with that of TIMP-2 protein. Negative correlation between expression of TIMP-1 protein and MMP-9 protein was found (P< 0.01). Overexpression of MMP-2 and MMP-9 protein were higher in breast cancers with lymph node metastases than those without lymph node metastases, whereas TIMP-2 mRNA and TIMP-1 protein expression were lower in breast cancers with lymph node metastases than those without lymph node metastases (P< 0.05). MMP-2 mRNA and MMP-9 protein were positively associated with the tumor size and shortened survival time(P< 0.05, P< 0.01). Increased expression of MMP-9 protein was correlated with high TNM classification(P< 0.01). The patients of menopause and ER negative expression had higher expression of MMP-2 mRNA (P< 0.05). Kaplan-Meier analysis showed that MMP-2 mRNA, MMP-2 and MMP-9 proteins were linked with unfavorable prognosis(P< 0.01,P< 0.05).

Conclusion: Overexpression of MMP-2, MMP-9 and expression imbalance between MMP-9 and TIMP-1 protein might play critical roles in degradation of extracellular matrix to enhance the invasive and metastatic capacity of breast cancer. MMP-2 protein might be applied as an independent prognostic indicator for primary breast cancer.