Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer

• Published in: Gynecologic oncology 2008-03, Vol.108 (3), p.569-576
• Main Authors: Steiner, E, Pollow, K, Hasenclever, D, Schormann, W, Hermes, M, Schmidt, M, Puhl, A, Brulport, M, Bauer, A, Petry, I.B, Koelbl, H, Hengstler, J.G
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adhesion; Biomarkers, Tumor - metabolism; Disease-Free Survival; Endometrial cancer; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - mortality; Endometrial Neoplasms - pathology; Endometrial Neoplasms - surgery; Female; Germany - epidemiology; Hematology, Oncology and Palliative Medicine; Humans; Metastasis; Middle Aged; Neoplasm Staging; Obstetrics and Gynecology; PAI-1; Plasminogen Activator Inhibitor 1 - metabolism; Predictive Value of Tests; Prognosis; Survival; Survival Analysis; Time to relapse; uPA; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2007.11.025

Abstract Background. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) contribute to the invasiveness of many carcinomas. Here, we studied a possible association between cytosolic uPA and PA-1 concentrations in tumor tissue with prognosis in patients with endometrial cancer. Methods. Cytosolic concentrations of uPA and PAI-1 were determined in 69 primary endothelial adenocarcinomas using an enzyme-linked immunoassay (ELISA). A possible influence of uPA and PAI-1 was studied by multivariate Cox regression adjusting for the established clinical prognostic factors FIGO-stage, grading, depth of invasion, diabetes mellitus and age. Results. Both uPA ( p = 0.011) and PAI-1 ( p = 0.003) were associated with relapse free time using the multivariate proportional hazards model. Association with overall survival was less pronounced with p = 0.021 for uPA and p = 0.358 for PAI-1. Concentrations of PAI-1 increased with FIGO stage ( p = 0.003) and with histological grading ( p = 0.005). Both uPA and PAI-1 concentrations were negatively correlated with estrogen and progesterone receptor levels. Conclusion. The combination of high cytosolic concentrations of uPA (> 5 ng/mg total protein) and high PAI-1 (> 20 ng/mg total protein) may reveal a group of patients with increased risk of progression.