PURPOSE: An extensive body of literature regarding p53 has accumulated during 
the last 2 decades. The cellular mechanisms of p53 are complex yet well-defined, 
whereas its clinical usefulness in the management of bladder cancer remains 
controversial. We outline the basic constitutive functions of p53 and summarize 
its current role in the management of transitional cell carcinoma of the 
bladder.
MATERIALS AND METHODS: We conducted a MEDLINE based literature review concerning 
the fundamental mechanisms of p53 and its role in the management of bladder 
cancer.
RESULTS: The p53 gene is a tumor suppressor gene that acts as "guardian of the 
genome." Many diverse cellular events, including DNA damage and hypoxia, 
activate the p53 gene. The p53 protein functions as a transcription factor, 
regulating downstream genes involved in cell cycle arrest, DNA repair and 
programmed cell death. Loss of p53 function confers genomic instability, 
impaired apoptosis and diminished cell cycle restraint. Therefore, p53 mutations 
select for certain critical features of malignancy. Alteration of P53 is the 
most common mutation in human cancer. Roughly half of all human malignancies, 
including many urological cancers, exhibit p53 mutations. In bladder cancer p53 
mutations have been associated with higher tumor grade and advanced stage, as 
well as progression of superficial disease to muscle invasion. Moreover, p53 
nuclear over expression appears to be an independent predictor of disease 
progression and decreased survival after cystectomy.
CONCLUSIONS: The importance of p53 mutation in tumor cell biology is 
irrefutable. Wild-type p53 mediates imperative functions such as regulation of 
the cell cycle and programmed cell death. Deficiency of p53 function by mutation 
or inactivation abrogates normal cell cycle checkpoints and apoptosis, 
generating a favorable milieu for genomic instability and carcinogenesis. 
However, despite the manifest importance of p53 in human malignancy, its current 
role in the management of bladder cancer appears somewhat limited. A multitude 
of retrospective studies have associated p53 mutations with adverse outcomes in 
superficial and muscle invasive disease. Nonetheless, randomized prospective 
studies are needed to determine the potential clinical implications of p53 in 
bladder cancer.