Abstracts
2000 Digestive Disease Week

# 2229 Increased Expression of Membrane Type 1-Matrix Metalloprotease (MT1- MMP) Is Found as Normal Colonic Mucosa (NM) Progresses Through Adenoma and Carcinoma-In-Situ (CIS) to INVasive Carcinoma (Inv).
Sandeep Malhotra, David Eisenberg, John Scholes, Rosemary Wieczorek, Peter Shamamian, Elliot Newman, New York, NY

BACKGROUND: MT1-MMP is a membrane associated metalloproteinase which is involved in the degradation of basement membrane collagen via the activation of MMP-2. While it has been shown to be over expressed in invasive colon cancer, its presence in adenomatous polyps or preinvasive colonic lesions, is less well defined. HYPOTHESIS: Most colonic adenocarcinomas originate from preexisting adenomatous polyps which progress through preinvasive CIS to invasive carcinoma. Since tumor cell invasion through the basement membrane is one of the critical cellular events in neoplastic progression, there is an upregulation in the expression of MT1-MMP as NM sequentially progresses to adenoma, CIS and INV. METHODS: Immunoperoxidase staining was performed on paraffin sections of specimens containing NM, adenoma,CIS and INV using mouse monoclonal antibody to human MT1-MMP. Non-immune mouse serum served as a negative control. Cultured human fibrosarcoma cells transfected with MTI-MMP cDNA served as positive controls. Staining for MT1-MMP was graded from 0 to 3+ for both distribution and intensity independently. Final MT1-MMP score was the product of the two scores with a range of 0 to 9. Mean scores for the groups were compared using the Wilcoxon test. Significance defined as p<0.05. RESULTS: The mean MT1-MMP scores for both adenoma and CIS were significantly greater than that of NM yet less than that of invasive cancer as summarized in the attached table. CONCLUSION: Colonic adenomas and preinvasive lesions upregulate expression of MT1-MMP compared to NM. Further upregulation contributes to the eventual development of invasive carcinoma in the “adenoma - carcinoma” sequence.