the p53 DATABASE

The p53gene encodes a 53kDa transcription factor with a criticalrole in DNA repair and apoptosis. Mutated p53 proteinhas a much longer half-life than wild-type p53, thusallowing its detection by immunohistochemistry.Approximately 50% of muscle-invasive TCCs shownuclear overexpression of p53 indicating presence of amutated protein. This is associated with increased stageand grade. It appears that in superficially invasive disease(T1), although p53 mutant expression occurs lessfrequently, it is associated with poorer outcome and ahigher rate of disease progression. Altered p53 status isalso a predictor of decreased survival. In muscle-invasiveTCC, it has been associated with a doubling in therisk of death from BC. Furthermore, altered p53 is frequentlyassociated with carcinoma in situ and its pooreroutlook, thus supporting the argument that p53 hasa role in a path to BC development and progression inhigh-grade TCCs.

Although it appears that altered p53 status is associatedwith a poorer prognosis, the practical clinicalimplications need to be further elucidated. For example,it is uncertain whether p53 status is helpful in predictingresponses to chemotherapy or surgery. Sarkis etal showed that altered p53 was an independent prognosticmarker for survival and an indicator of treatmentfailure in patients with invasive BC treated with neoadjuvantM-VAC (methotrexate, vinblastine, doxorubicin,and cisplatin) therapy. Conversely, Cote and coworkers44 found that the only group of patients with localand regionally extensive TCC who benefited from cisplatin-based adjuvant chemotherapy had abnormal p53expression. Moreover, Glick et al could not predict byp53 status which patients would eventually sufferrecurrence or die after cystectomy and thus could notstratify patients to those who would benefit from a cystectomy.Further confounding the widespread adoptionof p53 status as a determinant of treatment is disagreementabout how many tumor cells need to displaynuclear overexpression of p53 to have prognostic utility.Similarly, technical factors including antibodies usedto detect p53, means of tissue preservation (eg, formalinfixed or frozen), and methods of enhancing antigendetection and quantification have differed from studyto study.