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Urokinase-type plasminogen activator receptor in gastric cancer: tissue expression and prognostic role
Authors:Mario Plebani  Làszlo Herszènyi  Paolo Carraro  Massimo De Paoli  Giovanni Roveroni  Romilda Cardin  Zsolt Tulassay  Remo Naccarato  Fabio Farinati
Affiliation:(1) Dipartimento di Medicina di Laboratorio, Laboratorio Centrale, Istituto di Medicina Interna, Università di Padova, Padova, Italy;(2) Cattedra Malattie Apparato Digerente, Istituto di Medicina Interna, Università di Padova, Padova, Italy;(3) Second Department of Medicine, Semmelweis University Medical School Budapest, Budapest, Hungary
Abstract:The urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 are thought to play an important part in gastric cancer (GC) invasion and metastasis. Little is known about the behavior and prognostic impact of the receptor for UPA (UPAR). The aims of the present study were: (1) to measure UPAR, UPA and PAI-1 levels in GC and in non-malignant tissue distant from the tumor (NORM); (2) to evaluate their relationship with histomorphological parameters; and (3) to determine their prognostic value. UPAR, UPA and PAI-1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery. The GC was also examined in terms of the presence (n=10) or absence (n=10) of metastasis, differentiation (five differentiated, 15 undifferentiated) and histotype. Survival was analysed using life table analysis. UPAR, UPA and PAI-1 were significantly higher in GC vs NORM, in the presence of metastasis (UPAR, UPA) and in undifferentiated GC (UPAR, PAI-1). UPAR significantly correlated with UPA and PAI-1. Low levels of UPAR (P=0.04), UPA (P=0.007) and PAI-1 (P=0.02) were associated with a better survival. Our results demonstrate a sharp increase in UPAR in GC and suggest a prognostic role for it. The concomitant activation of UPAR, UPA and PAI-1 in GC confirm the important role of the plasminogen activator system in the process of invasion and metastasis.
Keywords:gastric cancer  plasminogen activator inhibitor type-1  urokinase receptor  urokinase-type plasminogen activator
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