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Vol. 65, No. 4, 2003
Issue release date: December 2003
Oncology 2003;65:363–370

Seprase, a Membrane-Type Serine Protease, Has Different Expression Patterns in Intestinal- and Diffuse-Type Gastric Cancer

Okada K. · Chen W.-T. · Iwasa S. · Jin X. · Yamane T. · Ooi A. · Mitsumata M.
aFirst Department of Pathology, Yamanashi University Faculty of Medicine, Tamaho, Nakakoma-gun, Yamanashi, and bDepartment of Pathology, Nihon University School of Medicine, Itabashi, Tokyo, Japan; cDepartment of Medicine, State University of New York, Stony Brook, N.Y., USA

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Objective: Seprase is an integral membrane serine proteinase with gelatinase activity that may be involved in cancer invasion and metastasis. However, the pathophysiologic significance of its expression in gastric cancer tissue has not been fully elucidated. Methods: Seprase expression and distribution in gastric cancer specimens obtained from 133 patients were examined by immunohistochemistry and immunoblotting. Results: Immunohistochemistry showed that in intestinal-type cancer, which includes well and moderately differentiated adenocarcinoma, seprase immunoreactivity was mainly recognized in the moderately differentiated cells and not in the well differentiated cells. In the diffuse type, which includes poorly differentiated adenocarcinoma and signet ring cell carcinoma, seprase immunoreactivity was seen mainly in cells with poor cell-to-cell junctions. The reactive pattern in the cells was different between moderately differentiated adenocarcinoma and diffuse-type carcinoma. Besides the cytoplasm, the cell membrane also apparently reacted in the former, while only the cytoplasm reacted diffusely in the latter. Seprase immunoreactivity was also recognized in endothelial cells and stromal cells especially adjacent to tumor nests. The immunoreactivity of the stromal cells was more abundant in the intestinal type than in the diffuse type, and these stromal expressions of seprase in the intestinal type correlated with the liver (13/13 = 100% of cases with metastases) or lymph node metastases (33/34 = 97% of cases with metastases). Immunoblotting showed that the levels of seprase protein were higher in intestinal-type cancer than in diffuse-type cancer. Conclusion: These results suggested that there is a difference in seprase expression between intestinal- and diffuse-type gastric cancer; this difference may reflect distinct biological features of these types of cancer.

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