Type 1 plasminogen activator inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC) and its impact on angiogenesis, progression and patient survival after radical nephrectomy

BMC Urol. 2010 Dec 3:10:20. doi: 10.1186/1471-2490-10-20.

Abstract

Background: To examine the expression of type 1 plasminogen inhibitor (PAI-1) in clear cell renal cell carcinoma (CCRCC), and its possible association with microvessel density (MVD), the expression of thrombospondin-1 (TSP-1), nuclear grade, tumour stage, continuously coded tumour size (CCTS) and to assess the value of PAI as a prognostic marker in 162 patients with CCRCC treated with radical nephrectomy.

Methods: A total of 172 consecutive patients with CCRCC treated with radical nephrectomy were enrolled in the study. The expression of PAI-1, TSP-1 and factor VIII were analysed on formalin-fixed, paraffin-embedded tissues without knowledge of the clinical outcome. Ten cases, where PAI-1 immunohistochemistry was not possible due to technical problems and lack of material, were excluded. Sixty-nine patients (43%) died of RCC, while 47 patients (29%) died of other diseases. Median follow-up was 13.8 years for the surviving 46 patients (28%).

Results: Nine percent of the tumours showed PAI-1 positivity. High expression of PAI-1 was significantly inversely correlated with TSP-1 (p = 0.046) and directly with advanced stage (p = 0.008), high NG (3+4) (p = 0.002), tumour size (p = 0.011), microvessel density (p = 0.049) and disease progression (p = 0.002). In univariate analysis PAI-1 was a significant prognosticator of cancer-specific survival (CSS) (p < 0.001). Multivariate analysis revealed that TNM stage (p < 0.001), PAI-1 (p = 0.020), TSP-1 (p < 0.001) and MVD (p = 0.007) were independent predictors of CSS.

Conclusions: PAI-1 was found to be an independently significant prognosticator of CSS and a promoter of tumour angiogenesis, aggressiveness and progression in CCRCC.

Publication types

  • Clinical Trial

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Renal Cell* / blood supply
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / mortality
  • Carcinoma, Renal Cell* / surgery
  • Disease Progression
  • Factor VIII / metabolism
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms* / blood supply
  • Kidney Neoplasms* / complications
  • Kidney Neoplasms* / metabolism
  • Kidney Neoplasms* / mortality
  • Kidney Neoplasms* / surgery
  • Neoplasm Staging
  • Neovascularization, Pathologic* / metabolism
  • Nephrectomy
  • Plasminogen Activator Inhibitor 1* / metabolism
  • Proportional Hazards Models
  • Serine Proteinase Inhibitors / metabolism
  • Thrombospondin 1 / metabolism

Substances

  • Biomarkers, Tumor
  • Plasminogen Activator Inhibitor 1
  • Serine Proteinase Inhibitors
  • Thrombospondin 1
  • Factor VIII