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Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging

Nature Clinical Practice Urology volume 3, pages 642–652 (2006)Cite this article

Abstract

Molecular biology is expected to provide new tools and approaches to assess the prognosis of patients with bladder cancer, by providing information on the risks of tumor recurrence and progression from superficial bladder cancer to an invasive phenotype. Genetic and epigenetic alterations have been closely associated with bladder carcinogenesis and progression, although most of these are still under investigation in a preclinical setting. This article highlights current findings from molecular studies, and describes their potential application in molecular staging of bladder cancer.

Key Points

  • Activating mutations in oncogenes such as HRAS and in FGFR3 are reported in bladder cancer; in particular, a mutation of FGFR3 is evident in 70% of superficial bladder cancers of pTa stage

  • TP53 and RB1 genes are key regulators of the cell cycle, and mutations of TP53 are frequently found in high-grade, high-stage bladder cancers

  • Overexpression of p53 is thought to be a poor prognostic indicator in bladder cancer, although considerable variation in p53 expression is reported, depending on the assay conditions

  • Ki-67 antigen is expressed in the nucleus of proliferating cells and the labeling index of Ki-67 expression (measured by immunostaining using MIB-1 monoclonal antibody) is thought to be a prognostic marker for bladder cancer

  • Chromosome losses are available as markers of bladder cancer; loss of chromosome 9 is the most frequent genetic alteration in bladder cancer, and loss of 17p or the TP53 locus is observed in most invasive bladder cancers

  • Genome-wide DNA analysis, using gene chips or complementary DNA arrays, are powerful tools for data mining, but further statistical validation is required before these tools can have clinical applications in cancer staging

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Figure 1: Outline of the molecules resulting in genetic and/or epigenetic alterations in transitional cell carcinoma of the bladder described in this article.
Figure 2: The allelic status of the ABO gene (which encodes transferase A, alpha 1-3-N-acetylgalactosaminyltransferase and transferase B, alpha 1-3-galactosyltransferase) has been analyzed in bladder cancers.

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Acknowledgements

We thank Dr Yoshitomo Chihara for his cooperation in preparing experimental data. This work was supported in part by Grants-in-Aid for Cancer Research, and for the Third Term Comprehensive 10-year Program for Cancer Control from the Ministry of Health, Labour and Welfare, Japan.

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Authors and Affiliations

  1. Chief Investigator in the Oncogene Research Unit/Cancer Prevention Unit in Tochigi Cancer Center Research Institute, Utsunomiya

    Kokichi Sugano

  2. Director of the National Cancer Center, Tokyo, Japan

    Tadao Kakizoe

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Correspondence to Tadao Kakizoe.

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Sugano, K., Kakizoe, T. Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging. Nat Rev Urol 3, 642–652 (2006). https://doi.org/10.1038/ncpuro0649

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