Desmoplastic response in scirrhous gastric carcinoma: imbalance between collagen synthesis and degradation.
BACKGROUND
Scirrhous gastric carcinoma is characterized by a marked deposition of collagen in the stroma and has a very poor prognosis.


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.


CONCLUSIONS
These data suggest that decreased collagenase activity and increased expression of TIMP-1 would result in collagen deposition in scirrhous gastric carcinoma tissue.
Matsui
H
H
Department of Surgery I, Fujita Health University, School of Medicine, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi 470-1192, Japan. hmatsui@fujita-hu.ac.jp
Kubochi
K
K
Shimada
A
A
Hasumi
A
A
D002293:Adenocarcinoma, Scirrhous / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D012016:Reference Values; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D011392:Proline; D011393:Procollagen-Proline Dioxygenase; D017364:Collagenases