EXPRESSION OF TISSUE INHIBITOR OF METALLOPROTEINASES TIMP-2 IN HUMAN COLORECTAL-CANCER - A PREDICTOR OF TUMOR STAGE

The aim of this study was to investigate whether immunohistochemical s taining 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 f rom 212 patients operated on between January 1987 and November 1990 we re 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 s troma with (c) subglandular enhancement was found significantly (P < 0 .01, P < 0.05, P < 0.05) more often in localized tumours than in tumou rs with regional or distant metastases. Neither pattern correlated wit h tumour differentiation. Patterns (a) and (c) correlated with longer survival time (P < 0.05); (b) reached near significance (P < 0.07). Wh en the survival analyses were restricted to potentially cured patients , neither pattern could foretell death from cancer. Positive expressio n of MMP-2 in tumour epithelium and of MMP-9 in tumour-infiltrating ma crophages were both independent of tumour stage and were without corre lation with survival time. A large number of MMP-9-positive macrophage s 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 discriminati on between macroscopically localized and metastatic colorectal cancer, but it cannot predict which of the potentially cured patients are lik ely to have micrometastases. MMP-2 and MMP-9 stainings are of minor va lue in staging and prognostic prediction.