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

Gynecol Oncol. 2008 Mar;108(3):569-76. doi: 10.1016/j.ygyno.2007.11.025. Epub 2008 Jan 28.

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.

Publication types

  • Evaluation Study

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Biomarkers, Tumor / metabolism*
  • Disease-Free Survival
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / surgery
  • Female
  • Germany / epidemiology
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis
  • Urokinase-Type Plasminogen Activator / metabolism*

Substances

  • Biomarkers, Tumor
  • Plasminogen Activator Inhibitor 1
  • Urokinase-Type Plasminogen Activator