Significance of Membrane Type 1 Matrix Metalloproteinase Expression in Breast Cancer

Abstract

Expression of matrix metalloproteinases (MMPs) plays an essential role in tumor metastasis and invasion through the degradation of extracellular matrix (ECM). MT1‐MMP (membrane type 1 matrix metalloproteinase), a membrane‐type MMP, is responsible for the activation of MMP2. In this study the significance of MT1‐MMP expression in human breast tumors was investigated by immunocytochemical assay, and its correlation with clinicobiological features was analyzed. MT1‐MMP expression was detected in tumor cells and/or stromal cells, and there was a strong correlation between the expressions of MT1‐MMP in the two cell types. Out of 183 primary tumors, 103 (56.2%) showed positive staining of MT1‐MMP in tumor cells. MT1‐MMP expression showed no significant correlation with any of the clinicobiological parameters examined, including hormone receptor status and angiogenesis. In postoperative survival analysis, MT1‐MMP expression itself was not a significant prognostic factor. However, in the particular subgroup with the accumulation of thymidine phosphorylase (TP)‐positive stromal cells, which have been activated by various stimuli, such as cytokines and hypoxia, MT1‐MMP expression had a significant prognostic value. These data suggested that MT1‐MMP might function cooperatively with tumor‐associated stromal cells for the progression of breast cancer.