Angiopoetin-2 (Ang-2), vascular endothelial growth factor receptors (VEGFRs) and CD31, a member of immunoglobulin superfamily, regulate normal vascular development and remodeling, as well as pathological neovascularization in cancer. The aim of this study was to investigate Ang-2 expression alone as single prognostic factor and in combination with other angiogenesis markers (VEGFR3 and CD31) and cell proliferation and survival markers (MIB-1 and BCL-2).
This study included 224 RCC patients whose nephrectomies were performed between 1985-1995 at Tampere University Hospital or Tampere Hospital. All tumor samples were re-evaluated and reclassified using Fuhrman grading system and Heidelberg classification. Two parallel multi tissue blocks were obtained fur further immunological analysis. Ang-2 expression was measured from digital images and positive area was expressed as the percentage of total tumor area. Ang-2 expression were categorized both by median into low (≤ 5.5) or high (>5.5) and by upper quartile into low (
The median age of patients was 65 years at the time of diagnosis. Higher Ang-2 expression was associated with lower tumor stage and grade, positive VEGFR3 and high BCL-2 expression, and low MIB-1 expression (p = 0.042, p = 0.018, p = 0.005, p = 0.013 and p = 0.039, respectively). RCC patients with very high Ang-2 expression associated with better survival in Kaplan-Meier analysis. Multivariate analysis showed that RCC patients having low Ang-2 expression or high MIB-1 expression had poorer survival: HR 1.89; 95% CI 1.16-3.08, p = 0.010, HR 2.20; 95% CI 1.36-3.54, p = 0.001 compared with high Ang-2 and low MIB-1 expression. However tumor stage and grade were still powerful prognostic factors.
Very high Ang-2 expression was associated with better survival in RCC patients. Ang-2 expression was a significant prognostic factor in multivariate analysis together with known prognostic factors, tumor stage and grade.
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Legal entity responsible for the study
Pirkanmaa Hospital District Science Center and the Academy of Finland Centre of Excellence Program.
P. Bono: Honoraria from Pfizer, novartis, Orion Pharma, BMS, MSD and research funding from Novartis. P-L. Kellokumpu-Lehtinen: Honoraria from Sanofi, Amgen, Bayer Eli Lilly and Researsch founding from Sanofi, Roche and Pfizer. All other authors have declared no conflicts of interest.