Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients

Abstract

Summary Matrix metalloprotease-9 (MMP-9; 92 kDa type IV collaganase, gelatinase B) is regarded as, important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodelling events. In this study we evaluate the prognostic value of MMP-9, by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 status was compared with the concentration of cytosolic Cathepsin-D and with other established prognostic factors, in terms of disease free survival and overall survival. The median follow-up period was 62 months. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P = 0.014), invasive ductal histologic (P = 0.037), progesterone receptor (PR)-negative and PRstrong positive tumours (P < 0.001), as well as samples belonging to patients with stage III-IV disease (P = 0.009) and age 45-55 years (P = 0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR = 0.45; P = 0.039) or death (RR = 0.32; P = 0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of OS (RR = 0.47; P = 0.034) in node-negative but not in node-positive patients. Our results suggest that MMP-9 may be an independent favourable prognostic factor in node-negative breast cancer patients. The overexpression of MMP-9 in breast cancer may be also used as a marker to subdivide node negative breast cancer patients in order to determine the optimal treatment modality.

Prognostic Value of Matrix Metalloproteinase 9 Expression in Breast Cancer Patients: A Meta-analysis

“…Subgroup analysis by location showed that a statistically significant impact of MMP-9 expression as a prognostic factor in both of tumor cells and stromal tissue. But we also noticed that some studies (Oscar et al, 2012;Tian et al, 2009;Vizosoet al, 2007;Li et al, 2006;Scorilas et al, 2001) combined the expression of tumor cells and stromal tissue to investigate the significance of MMP-9 expression, which made it difficult to explain which part of accumulation of MMP-9 played the most important influence on prognosis in breast cancer patients. Therefore, the impact of different location of MMP-9 expression on prognosis seems still needed to be further confirmed by adequately designed studies with multivariate analysis.…”

“…Furthermore, two studies (Pellikainen 2004;Gonzalez et al, 2010) provided information about MMP-9 expression in tumor cells and stromal tissues respectively without general result, which we treated independently. Eventually, 15 studies met the inclusion criteria were included (Scorilas et al, 2001;Fan et al, 2003;Li et al, 2004;Pellikainen et al, 2004;Rahko et al, 2004;Li et al, 2006;Mylona et al, 2007;Vizoso et al, 2007;Feng et al, 2008;Wu et al, 2008;Zhao et al, 2008;Tian et al, 2009;Gonzalez et al, 2010;Sullu et al, 2011;Oscar et al, 2012).…”

Gelatinase-mediated migration and invasion of cancer cells

“…In melanoma, increased expression of MMP-9 is found in the early steps, but at a later stage the opposite is true (van den Oord et al, 1997). In breast and colon cancer MMP-9 expression has been correlated with both increased and decreased survival and formation of distant metastasis (Pacheco et al, 1998;Scorilas et al, 2001;Takeha et al, 1997;Zeng et al, 1996). The current view is that the gelatinases and other MMPs are needed at multiple stages during the tumor progression and different tumors may utilize different MMPs.…”

Cooperation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness

“…Moreover, MMP-9 was detected more frequently in malignant breast carcinoma than in benign tumour (Rha et al, 1997;Hanemaaijer et al, 2000). However, the role of MMP-9 is less clear than that of u-PA, as overexpression of MMP-9 in human breast cancer was reported to be a favourable indicator in node-negative patients (Scorilas et al, 2001).…”