Despite the fact that the current histopathologic classification for bladder cancer has led to improved concepts for the clinical management of the disease, key questions with regard to assessment of risk for recurrence and/or progression to invasive disease remain. In addition, response to specific therapies cannot be predicted accurately. Bladder tumors comprise a heterogeneous group with respect to both histopathology and clinical behavior. Thus, it is anticipated that a thorough knowledge and interpretation of the molecular alterations involved in tumor development and progression will lead to greater prognostic and predictive power. This may not only lead to better comprehension of the biology of the disease, but may also lead to the development of novel individualized therapies. Novel means of stratification are urgently needed to provide a new subclassification of urothelial lesions. This review discusses and summarizes the genetic alterations that have been reported in bladder cancer and relates these to the current 2-pathway model for tumor development. The molecular pathogenesis of high-grade noninvasive papillary tumors and of T1 tumors is not yet clear, and possibilities are discussed.
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