How urinary bladder tumors grow and expand: The bladder as a model for the study of clonal organization and field cancerization

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Bladder cancer is one of the best models to study tumour development and pro-gression: 1) both genetic and environmental factors contribute as causes, 2) two major disease phenotypes (non-invasive papillary and invasive) have been recognized, 3) progression occurs following distinct genetic pathways, 4) multiple syn- or metachronous tumours are often found, and 5) a “field effect” has been reported in the non-neoplastic urothelium. In addition, bladder cancer is socially relevant, as it generates the highest costs/patient to the health system. In this project, the steps of tumour development and spread will be examined by focusing on the epithelial stem cell concept. We want to identify the urothelial stem cell location and trace the clonal progeny as well as its changes in different bladder cancer pheno-types. This will be carried out by a histochemical method to detect activity of cytochrome c oxidase, and mitochondrial and nuclear DNA-sequencing. This histo-morphological approach will allow for the first time two-dimensional insights into the growth and the development of bladder tumours and will help pathologists and clinicians to understand better such a versatile disease.