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.
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.
Department of Surgical Sciences, University of Bergen, Norway. dragomir.zubac@kir.uib.no
Dragomir P
DP
Zubac
Tore
T
Wentzel-Larsen
Tomas
T
Seidal
Leif
L
Bostad
D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D018450:Disease Progression; D005169:Factor VIII / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000098:blood supply / Q000150:complications / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009392:Nephrectomy; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D016016:Proportional Hazards Models; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D019700:Thrombospondin 1; D005169:Factor VIII