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

Abstract

PURPOSE:

Vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), and their receptor Tie2 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) than in normal 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.

• Authors: Tibor Szarvas, Tobias Jäger, Martin Tötsch, Frank vom Dorp, Carsten Kempkensteffen, Ilona Kovalszky, Imre Romics, Süleyman Ergün, Herbert Rübben
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 24 Pg. 8253-62 (Dec 15 2008) ISSN: 1078-0432 [Print] United States
• PMID: 19088043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ANGPT1 protein, human
• Angiopoietin-1
• Angiopoietin-2
• Vascular Endothelial Growth Factor A
• Receptor, TIE-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Angiopoietin-1 (analysis, genetics)
• Angiopoietin-2 (analysis, genetics)
• Female
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Multivariate Analysis
• Prognosis
• Receptor, TIE-2 (analysis, genetics)
• Urinary Bladder Neoplasms (blood supply, mortality)
• Vascular Endothelial Growth Factor A (analysis, genetics)