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

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

Research output: Contribution to journalArticle

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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

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Urinary Bladder Neoplasms
Vascular Endothelial Growth Factor A
Urinary Bladder
Confidence Intervals
Neoplasms
Epithelium
Angiopoietins
Pathologic Neovascularization
Angiopoietin-1
Proportional Hazards Models
Real-Time Polymerase Chain Reaction
Research Design
Multivariate Analysis
Immunohistochemistry
Neoplasm Metastasis
Recurrence
Cell Line
Survival
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Szarvas, T., Jäger, T., Tötsch, M., Dorp, F. V., Kempkensteffen, C., Kovalszky, I., ... 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

Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder cancer. / Szarvas, Tibor; Jäger, Tobias; Tötsch, Martin; Dorp, Frank Vom; Kempkensteffen, Carsten; Kovalszky, I.; Romics, I.; Ergün, L. Süleyman; Rübben, Herbert.

In: Clinical Cancer Research, Vol. 14, No. 24, 15.12.2008, p. 8253-8262.

Research output: Contribution to journalArticle

Szarvas, T, Jäger, T, Tötsch, M, Dorp, FV, Kempkensteffen, C, Kovalszky, I, Romics, I, Ergün, LS & Rübben, H 2008, 'Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder cancer', Clinical Cancer Research, vol. 14, no. 24, pp. 8253-8262. https://doi.org/10.1158/1078-0432.CCR-08-0677
Szarvas, Tibor ; Jäger, Tobias ; Tötsch, Martin ; Dorp, Frank Vom ; Kempkensteffen, Carsten ; Kovalszky, I. ; Romics, I. ; Ergün, L. Süleyman ; Rübben, Herbert. / Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder cancer. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 24. pp. 8253-8262.
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AU - Jäger, Tobias

AU - Tötsch, Martin

AU - Dorp, Frank Vom

AU - Kempkensteffen, Carsten

AU - Kovalszky, I.

AU - Romics, I.

AU - Ergün, L. Süleyman

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