Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder cancer

Tibor Szarvas, Tobias Jäger, Martin Tötsch, Frank Vom Dorp, Carsten Kempkensteffen, Ilona Kovalszky, Imre Romics, L. Süleyman Ergün, Herbert Rübben

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35 Citations (Scopus)

Abstract

Purpose: Vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and their receptorTie2 are critically involved in both normal and pathologic angiogenesis. The aim of this study was to explore the role of Ang-1, Ang-2,VEGF, and Tie2 in the development and progression of bladder cancer as well as to examine their prognostic value in this tumor type. Experimental Design: Tumor samples of 113 bladder cancer patients, normal bladder epithelium of 5 noncancer patients, and two low-grade (UMUC3 and RT4) and two high-grade (J82 and T24) bladder cancer cell lines were analyzed by quantitative real-time PCR. The expression data were analyzed performing Wilcoxon rank-sum and Kaplan-Meier log-rank tests as well as univariate Cox analyses and Cox proportional hazards regression model. Results: In tissues of noninvasive bladder tumors, Ang-1 expression was significantly lower (P < 0.001), whereas VEGF expression was significantly higher (P = 0.031) thaninnormal bladder tissue. These findings were also confirmed at the protein level by immunohistochemistry. In contrast, Tie2 and Ang-2 abundance in tumor did not differ significantly from that in normal bladder tissue. Multivariate analysis identified Ang-2 as a strong and independent predictor of tumor recurrence [hazard ratio (HR), 10.18; 95% confidence interval (95% CI), 2.69-38.49; P < 0.001] and Tie2 expression as an independent favorable prognostic factor for both metastasis (HR, 0.31;95% CI,0.11-0.89; P = 0.029) and disease-specific survival (HR, 0.25; 95% CI, 0.10-0.62; P = 0.003). Conclusions: These data show the strongest change in expression of VEGF and Ang-1 in superficial bladder cancer in comparison with normal bladder epithelium and the invasive tumor stages. The prognostic significance of Ang-2 and Tie2 underlines the essential role of angiopoietins-Tie2 system in progression of bladder cancer.

Original languageEnglish
Pages (from-to)8253-8262
Number of pages10
JournalClinical Cancer Research
Volume14
Issue number24
DOIs
Publication statusPublished - Dec 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Szarvas, T., Jäger, T., Tötsch, M., Dorp, F. V., Kempkensteffen, C., Kovalszky, I., Romics, I., Ergün, L. S., & Rübben, H. (2008). Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder cancer. Clinical Cancer Research, 14(24), 8253-8262. https://doi.org/10.1158/1078-0432.CCR-08-0677