MRNA Expression Levels And Prognostic Value Of 40 Angiogenic Genes In A Large Series Of 157 Bladder Tumors

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 14 Jun 2008 - 9:00 PDT

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ORLANDO, FL (UroToday.com) - During carcinogenesis, angiogenesis is a fundamental process allowing both tumor growth and metastatic spread. Actors of the angiogenesis pathways are targets for the new promising targeted therapies already used in several malignancies. In bladder cancer, anti-angiogenic molecules could also add to already existing treatment options. The aim of this study presented by French investigators was to evaluate the involvement of angiogenesis pathways in bladder carcinogenesis and identify new molecular markers having a prognostic implication.

The studies evaluated the expression levels of 40 genes involved in angiogenesis by quantitative real time RT-PCR in normal and tumoral human bladder samples. Tumors were obtained from 157 patients (25 women and 132 men, mean age 68 years), who underwent transurethral bladder resection or radical cystectomy between 2001 and 2005. All patients have signed a informed consent. Pathological tumor staging showed: 73 superficial TCC (30 low grade pTa (group II), 14 high grade pTa (group III) and 29 high grade pT1 (group IV)), and 84 muscle-invasive tumors, all high-grade (>pT2, group V).

VEGFA, MET, CXCR4, and IL8 were significantly overexpressed in tumor samples as compared to normal bladder tissue (p<0.01). VEGFA overexpressions were both significant in superficial and invasive tumor samples as compared to normal bladder tissue (p<0.01). MET mRNA overexpressions were significant when comparing low grade pTa tumors to normal bladder samples (p<0.01), whereas IL8 and CXCR4 overexpressions were significant when comparing aggressive tumors (pT1 or invasive) to pTa tumors (p<0.01). In univariate analysis VEGFA overexpression is associated with a poorer outcome in both overall and disease-free survival (p=0.011 and 0.026 respectively). Multivariate analysis retained T stage, N status, and VEGFA overexpression as independent prognostic factors in both overall and disease-free survival (p=0.02 and p=0.04 respectively for VEGFA).

These results suggest a major role for several pro-angiogenic genes in bladder carcinogenesis. There is therefore a potential interest of anti-angiogenic targeted therapies in bladder cancer, especially those steered against VEGFA. This study shows that VEGFA status could be used as a prognostic factor at the individual level, and as a guide for rationalized use of the costly anti-angiogenic targeted therapies.

Presented by Geraldine Pignot, MD, Ivan Bieche, MD, Sophie Vacher, MD, Rosette Lidereau, MD, Bernard Debre, MD, and Delphine Amsellem-Ouazana, MD, at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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