H Matsui1, K Kubochi, A Shimada, A Hasumi. 1. Department of Surgery I, Fujita Health University, School of Medicine, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. hmatsui@fujita-hu.ac.jp
Abstract
BACKGROUND: Scirrhous gastric carcinoma is characterized by a marked deposition of collagen in the stroma and has a very poor prognosis. MATERIALS AND METHODS: To elucidate the fibrotic mechanism in scirrhous gastric carcinoma, we measured the activities of the collagen synthetic enzyme, prolyl 4-hydroxylase (P4H) and the collagen degrading enzymes, interstitial collagenase and type IV collagenase, in tissue from patients with advanced gastric carcinoma. Concentrations of P4H and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the sera of patients with gastric carcinoma were measured using sandwich enzyme immunoassay systems. We performed immunohistochemical analysis for TIMP-1. RESULTS: Enzyme activities of P4H, interstitial collagenase and type IV collagenase in the tumor samples of scirrhous gastric carcinoma were significantly lower than those of non-scirrhous gastric carcinoma (p < 0.01). Serum concentration of TIMP-1 in patients with diffuse type carcinoma was significantly higher than in patients with intestinal type carcinoma and control subjects (p < 0.05). We demonstrated stromal expression of TIMP-1 in scirrhous gastric carcinoma tissue. CONCLUSION: These data suggest that decreased collagenase activity and increased expression of TIMP-1 would result in collagen deposition in scirrhous gastric carcinoma tissue.
BACKGROUND:Scirrhous gastric carcinoma is characterized by a marked deposition of collagen in the stroma and has a very poor prognosis. MATERIALS AND METHODS: To elucidate the fibrotic mechanism in scirrhous gastric carcinoma, we measured the activities of the collagen synthetic enzyme, prolyl 4-hydroxylase (P4H) and the collagen degrading enzymes, interstitial collagenase and type IV collagenase, in tissue from patients with advanced gastric carcinoma. Concentrations of P4H and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the sera of patients with gastric carcinoma were measured using sandwich enzyme immunoassay systems. We performed immunohistochemical analysis for TIMP-1. RESULTS: Enzyme activities of P4H, interstitial collagenase and type IV collagenase in the tumor samples of scirrhous gastric carcinoma were significantly lower than those of non-scirrhous gastric carcinoma (p < 0.01). Serum concentration of TIMP-1 in patients with diffuse type carcinoma was significantly higher than in patients with intestinal type carcinoma and control subjects (p < 0.05). We demonstrated stromal expression of TIMP-1 in scirrhous gastric carcinoma tissue. CONCLUSION: These data suggest that decreased collagenase activity and increased expression of TIMP-1 would result in collagen deposition in scirrhous gastric carcinoma tissue.