title: Prognostic relevance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in gastric cancer.
abstract: Expression of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) was evaluated in 125 surgically resected gastric cancers by immunohistochemical analysis. Tissue was stained immunohistochemically with a monoclonal antibody against human uPA and monoclonal antibodies against human PAI-1 and PAI-2. In addition, DNA ploidy patterns were determined by cytofluorometer after staining with propidium iodide. We found that 82 (66%) of the 125 gastric cancers expressed uPA as diffuse cytoplasmic staining, as intensely outlined luminal borders. PAI-1 expression was observed in 62 (50%) of 125 gastric cancer as a fine, diffuse and granular pattern in the cytoplasm. PAI-2 expression was observed in 65 (52%) of the 125 gastric cancers as a diffuse cytoplasmic staining. uPA-positive tumours showed a higher incidence of infiltration, lymph node metastasis and peritoneal dissemination that uPA-negative ones. Patients with uPA-positive tumours proved to have a significantly poorer prognosis than those with negative ones. PAI-1-negative tumours showed a higher incidence of liver metastasis and carried a poorer prognosis than PAI-1-positive ones. There was no significant correlation between uPA or PAI-1 expression and DNA ploidy patterns. Conversely, there was no significant relationship between PAI-2 expression and clinicopathological parameters and prognosis. According to the expression of uPA and PAI-1 status, groups of 19 uPA(-)/PAI-1(-), 44 uPA(+)/PAI-1(-), 23 uPA(-)/PAI-1(+) and 39 uPA(+)/PAI-1(+) were subdivided. Tumours with uPA(+)/PAI-1(-) had a significantly higher incidence of liver metastasis, lymph node metastasis and serosal invasion than the other groups of tumours. Patients with uPA(+)/PAI-1(-) tumours had a significantly poorer prognosis than those with uPA(-)/PAI-1(+) tumours. These results indicate that uPA expression is a useful biological prognostic indicator, and that uPA expression is a useful biological prognostic indicator, and that uPA and PAI-1 may play an important part in the tumour progression and metastasis in gastric cancer.
authors.affiliation: The Second Department of Surgery, School of Medicine, Kanazawa University, Ishikawa, 920 Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Yonemura
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: K
authors.initials: K
authors.lastname: Tsuchihara
authors.forename: T
authors.initials: T
authors.lastname: Kawamura
authors.forename: N
authors.initials: N
authors.lastname: Nojima
authors.forename: T
authors.initials: T
authors.lastname: Fujimura
authors.forename: H
authors.initials: H
authors.lastname: Nose
authors.forename: Y
authors.initials: Y
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis*; D011003:Ploidies; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D014568:Urokinase-Type Plasminogen Activator