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MMP-1 is a Prognostic Marker for Hematogenous Metastasis of Colorectal Cancer

^a Department of Surgical Oncology; ^b Department of Transfusion Medicine, Graduate School of Medical Sciences, Faculty of Medicine, the University of Tokyo, Tokyo, Japan; ^c Institute of Molecular and Cellular Biosciences, the University of Tokyo, Tokyo, Japan; ^d Cancer Institute Hospital,Tokyo, Japan

Correspondence: Eiji Sunami, M.D., Department of Surgical Oncology, Graduate School of Medical Sciences, Faculty of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Telephone: +81-3-5800-8653; Fax: +81-3-3811-6822.

Background. Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. MMP-1 is a member of collagenases, a family of MMPs that degrades collagens type I, II, and III, main components of the interstitial stroma.

The purpose of this study was to investigate the expression of MMP-1 in colorectal cancer and its correlation with hematogenous metastasis.

Patients and Methods. We examined 133 cases of colorectal cancer (Dukes A: 72; Dukes B: 26; Dukes C: 23; Dukes D: 12). Sections were cut from formalin-fixed, paraffin-embedded samples containing the deepest site of cancer invasion and stained immunohistochemically with a monoclonal antibody to MMP-1. According to the area of the tumor that was stained, patients were divided into high- and low-MMP-1 expression groups.

Results. MMP-1 expression was observed in the cytoplasm of cancer cells, some stromal cells, and a few normal epithelial cells of colonic mucosa. High MMP-1 expression was found in 47 (35.3%) cases and low in 86 (64.7%). Hematogenous metastasis was identified in 14 (29.8%) of high-MMP-1 groups and 12 (13.9%) of low-MMP-1 groups. MMP-1 expression significantly correlated with hematogenous metastasis of colorectal cancer, but no correlation was found between MMP-1 expression and the other clinicopathological features investigated.

Conclusions. MMP-1 expression may be a novel marker for hematogenous metastasis of colorectal cancer, and its inhibition may be a strategy for prevention of metastasis.

Key Words. MMP-1 • Colon cancer • Hematogenous metastasis • Immunohistochemistry

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