Alterative Expression of Matrix Metalloproteinase 9 (Gelatinase B) during Colorectal Tumor Development and Progression

Yutaka Ogata, Tatsuhisa Morodomi, Akira Ookita, Kazuo Shirouzu, Hiroharu Isomoto, Teruo Kakegawa

First Department of Surgery, Kurume University School of Medicine

We have studied the expression of matrix metalloproteinase 9 (MMP-9/gelatinase B) in colorectal tumors at various developmental stages. A Total of 26 adenoma, 23 early stage colorectal adenocar. cinoma and 88 advanced cancer specimens were each fixed in formalin and embedded in paraffin. Then 3µm sections were examined by immunohistochemical technique (avidin-biotin peroxydase complex method) using anti-human MMP-9 sheep IgG, MMP-9 was demonstrated in tumor cells, neutrophils and monocyte-macrophages in colorectal tumor tissue. Whereas normal epithelial cells of colonic mucosa remote from the tumor were consistently negative for MMP-9, mucosal epithelial cells in close association with adenoma or adenocarcinoma were often positive for this enzyme. The incidence of MMP-9 expression was 9% in mucosal epithelial cells, 23% in adenoma cells, 43% in early stage adenocarcinoma cells, and 52% in advanced adenocarcinoma cells. In advanced cancers, the incidence of MMP-9 expression in the tumor cells was 83% in cases associated with synchronous liver metastasis, 58% in cases of metachronous liver metastasis, and 32% in cases without liver metastasis. The rate of MMP-9 expression in tumor cells was increased with decreasing grade of histological differentiation. However, there was no relationship between MMP-9 expression in tumor cells and other histopathological factors. These results suggested that MMP-9 was expressed according to tumor development and progression, and that MMP-9 produced in tumor cells may play an important role in hematogenous metastasis in colorectal cancer.

Key words
matrix metalloproteinase 9, gelatinase B, colorectal cancer, liver metastasis, immunohistochemistry

Reprint requests
Yutaka Ogata First Department of Surgery, Kurume University School of Medicine
67 Asahimachi, Kurume City, 830 JAPAN

Accepted
July 5, 1995

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