Expression of tissue inhibitor of metalloproteinases TIMP-2 in human colorectal cancer--a predictor of tumour stage

Abstract

The aim of this study was to investigate whether immunohistochemical staining patterns of tissue inhibitor of metalloproteinases TIMP-2 and matrix metalloproteinases MMP-2 and MMP-9 can be predictors of tumour stage and survival time in colorectal cancer. Frozen tumour sections from 212 patients operated on between January 1987 and November 1990 were investigated. Three mouse monoclonal antibodies--T2-101 against TIMP-2, CA-4001 against MMP-2 and GE-213 against MMP-9--were used. Positive expression of TIMP-2 (a) in basement membranes and (b) diffusely in stroma with (c) subglandular enhancement was found significantly (P < 0.01, P < 0.05, P < 0.05) more often in localized tumours than in tumours with regional or distant metastases. Neither pattern correlated with tumour differentiation. Patterns (a) and (c) correlated with longer survival time (P < 0.05); (b) reached near significance (P < 0.07). When the survival analyses were restricted to potentially cured patients, neither pattern could foretell death from cancer. Positive expression of MMP-2 in tumour epithelium and of MMP-9 in tumour-infiltrating macrophages were both independent of tumour stage and were without correlation with survival time. A large number of MMP-9-positive macrophages correlated (P < 0.05) with poor tumour differentiation, whereas weak or absent epithelial MMP-2 staining reached near significance (P < 0.08). Exploration of TIMP-2 expression is valuable for the discrimination between macroscopically localized and metastatic colorectal cancer, but it cannot predict which of the potentially cured patients are likely to have micrometastases. MMP-2 and MMP-9 stainings are of minor value in staging and prognostic prediction.