title: Cellular distribution and clinical value of urokinase-type plasminogen activator, its receptor, and plasminogen activator inhibitor-2 in esophageal squamous cell carcinoma.
abstract: To assess the participation of the plasminogen activation system in the invasiveness of esophageal squamous cell carcinoma, we performed immunohistochemistry and in situ hybridization to study the distribution of a urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR), and plasminogen activator inhibitor-2 (PAI-2). u-PA and PAI-2 were expressed heterogeneously in cancer cells, and restricted expression was found in stromal cells, especially fibroblasts, that were located in the immediate proximity of the cancerous cells. u-PAR was found only in cancer cells located at the periphery of tumors. Compared with patients with u-PA-negative cancer cells, patients with u-PA-positive cancer cells more frequently showed a neoplastic invasion beyond the muscularis propria and lymph node metastases. They also showed a significantly shorter 5-year overall survival. Patients with PAI-2-positive fibroblasts showed significantly lower levels of local invasiveness, represented by a neoplastic invasion beyond the muscularis propria, than those who were PAI-2 negative. Our results suggest that the expression of u-PA in esophageal squamous cell carcinoma is predictive of poor survival, whereas the expression of PAI-2 in the fibroblasts surrounding them is protective. An analysis of u-PA and PAI-2 expression in cancer cells and their surrounding fibroblasts may be useful for predicting the prognosis of patients with esophageal squamous cell carcinoma.
authors.affiliation: First Department of Surgery, Intensive Care Unit, Shiga University of Medical Science, Otsu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shiomi
authors.forename: Y
authors.initials: Y
authors.lastname: Eguchi
authors.forename: T
authors.initials: T
authors.lastname: Tani
authors.forename: M
authors.initials: M
authors.lastname: Kodama
authors.forename: T
authors.initials: T
authors.lastname: Hattori
mesh_terms: D000328:Adult; D000368:Aged; D000941:Antigens / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D016019:Survival Analysis; D014018:Tissue Distribution; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000941:Antigens; C524898:PLAUR protein, human; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator