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SHR Neuro Cancer Cardio Lipid Metab Microb

Szarvas, T; Jäger, T; Tötsch, M; vom Dorp, F; Kempkensteffen, C; Kovalszky, I; Romics, I; Ergün, S; Rübben, H.
Angiogenic switch of angiopietins-Tie2 system and its prognostic value in bladder cancer.
Clin Cancer Res. 2008; 14(24):8253-8262 Doi: 10.1158/1078-0432.CCR-08-0677 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Tötsch Martin
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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.
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Aged, 80 and over -; Angiopoietin-1 - analysis Angiopoietin-1 - genetics; Angiopoietin-2 - analysis Angiopoietin-2 - genetics; Female -; Humans -; Immunohistochemistry -; Male -; Middle Aged -; Multivariate Analysis -; Prognosis -; Receptor, TIE-2 - analysis Receptor, TIE-2 - genetics; Urinary Bladder Neoplasms - blood supply Urinary Bladder Neoplasms - mortality; Vascular Endothelial Growth Factor A - analysis Vascular Endothelial Growth Factor A - genetics