Do multifocal or recurrent urothelial carcinomas originate from a single transformed cell or from multiple transformed cells? What is the clinical significance of this argument?


Currently two hypotheses are being considered for the origin of multifocal or recurrent urothelial carcinomas. The clonogenic hypothesis (hypothesis 1) describes tumors as descendants of a single transformed cell that undergoes further multiple genetic alterations, proliferates, and spreads through the urothelial tract either by intraepithelial migration or intraluminal seeding. The “field changes” hypothesis (hypothesis 2) states that urothelial cells undergo malignant transformation at multiple sites and become the source of multifocal tumors. Based on reports with several available techniques, both hypotheses are viable to account for human bladder carcinogenesis. Hypothesis 1 may apply most of the urothelial carcinomas that result from exposure to the conventional carcinogen source (cigarette smoking). The underlying mechanism responsible for oligoclonal tumor development (hypothesis 2) remains unknown. It would be intriguing to suggest that heavy carcinogen exposure (e.g., aromatic amines, irradiation, heavy smoking) may cause the “field changes.”


Bladder Cancer Bladder Tumor Transitional Cell Carcinoma Urothelial Carcinoma Human Bladder Cancer 


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