Carcinogenetic Pathway of Urothelial Carcinoma

  • Shohreh Iravani Dickinson
Part of the Cancer Growth and Progression book series (CAGP, volume 12)


Two discrete molecular pathways of bladder carcinogenesis are recognized, one leading to superficial papillary carcinoma and the other to more aggressive either flat (carcinoma in situ) or invasive carcinoma. The majority of aggressive urothelial carcinomas show alterations in the p53 (TP53)-Mdm2-p14 and the retinoblastoma (Rb)-p16 genes and pathways. Both p53 and Rb maintain cellular homeostasis and control normal cell cycle, cellular growth and proliferation. In response to cellular stress, Rb is the main regulator of cell cycle progression, while p53’s main function is to trigger apoptosis or growth arrest in the G1 phase. Tumor angiogenesis also plays a role in urothelial carcinoma progression by providing oxygen, nutrients and growth factors to the neoplastic cells. Distinct genetic events portray the interaction between the molecules involved in these pathways, lending to their use as prognostic indicators. Patients with unaltered wild type p53 and Rb bladder cancers show significant decreased risk of recurrence and mortality when compared to those who have mutational alteration in both p53 and Rb. Alterations of p53 and Rb may help identify patients with high risk superficial cancers more likely to progress to invasive carcinoma or to identify patients who may fail conventional treatment. These patients may benefit from therapies targeting specific altered pathway molecules. Within the past several years, components of these pathways have been shown to be important prognostic and therapeutic response indicators and probable therapeutic targets.


Epidermal Growth Factor Receptor Bladder Cancer Urothelial Carcinoma TP53 Gene Bladder Carcinogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Department of PathologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

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