MATRIX METALLOPROTEINASE-1 IS ASSOCIATED WITH POOR-PROGNOSIS IN COLORECTAL-CANCER

Colorectal cancer is one of the commonest malignant tumors and has a r elatively poor prognosis. The outcome depends on the extent of local a nd particularly metastatic tumor spread. The matrix metalloproteinases (MMPs) are a family of closely related enzymes that degrade the extra cellular matrix and are considered to be important in facilitating tum or invasion and spread(1-3). Using immunohistochemistry we have invest igated the occurrence in colorectal cancer of MMP-1 (interstitial coll agenase). Our monoclonal antibody was prepared against a synthetic pep tide corresponding to an amino acid sequence specific for MMP-1 and wa s selected to react in formalin-fixed wax-embedded sections, thus allo wing use in diagnostic histopathology and also enabling access to arch ival material. We found that the presence of MMP-1 in colorectal cance r is associated with a poor prognosis (P = 0.006) and has prognostic v alue independent of Dukes stage. One MMP inhibitor that strongly inhib its MMP-1 has already been shown to inhibit growth of human colon canc er xenografts in nude mice(4). Our results suggest that treatment of t hose individuals whose colon tumors produce MMP-1 with MMP inhibitors is a therapeutic strategy worth pursuing.