Significance of Increased Expression of the Tissue Inhibitor of Matrix Metalloproteinase-2 in Human Colorectal Carcinomas

ABSTRACT

BACKGROUND: Tumor invasion and metastasis are the major causes of morbidity and death for cancer patients. Metastasis is a complex multistep process in which tumor cells must pass through supporting structures. Proteolytic degradation of the structures is an important part of this process, and matrix metalloproteinase (MMP) has been implicated. The activation and the enzymatic activity of MMP is regulated by the tissue inhibitor metalloproteinase (TIMP). Three distinct TIMP molecules have been isolated. Very little is known about the role of TIMP-2 in tumors. The purpose of this study was to examine the expression of TIMP-2 in human colorectal carcinomas. METHODS: The paraffin blocks of 33 colorectal carcinomas were recalled and immunostained with monoclonal antibodies specific for TIMP-2. The rate of stain was estimated, and the relationships between the expression and the stage, the differentiation, and the recurrence were assessed. RESULTS: The expression of TIMP-2 in tumor tissues increased with increasing Dukes's stage (p<0.05) and recurred cases (p<0.05). CONCLUSIONS: Our results suggest that increased expression of TIMP-2 may be useful as a marker of biologic aggressiveness.