The significance of p53 protein overexpression in T1 transitional cell carcinoma of the bladder as a marker for disease progression

Chung, Jin Soo; Lee, Sang Eun

Abstract

P53 is a tumor suppresser gene located on chromosome 17p. Mutations or allelic loss al this locus are the most frequent genetic abnormalities found in human cancer and the incidence of p53 gene mutation appeared to be much higher in invasive type and higher grade bladder cancer than in superficial and lower grade ones. To investigate the prevalence of altered patterns of p53 nuclear expression in T1 transitional cell carcinoma of the bladder and the hypothesis that altered patterns of expression or the protein product of the mutated p53 tumor suppresser gene are associated with tumor progression in patient with T1 transitional cell carcinoma of the bladder, we examined deparaftinized tumor tissue specimens from transurethral resection in forty nine patients with T1 bladder cancer. Nuclear overexpression of p53 protein was detected by immunohistochemical analysis using the mouse monoclonal antibody DO-7, which stain both wild-type and mutant pS3 protein using a standard avidin-biotin immunoperoxidase method. In forty nine patients, follow-up ranged from 30 to 70 months with mean of 45 months. During this period 11 patients had disease progrgssion. All variables other than p53 expression, such as age, tumor grade, previous history of T1 disease and BCG intravesical therapy failed to show good predictor of disease progression. When we divided two groups according to 20% and 50% cut-off value of p53 positivity in total population and grade 2 subgroup, p53 expression had ability to predict pregression at statistically significant level(p<0.05) with 50% cut-off value in total population and 20% and 50% cut-off value in grade 2 subgroup. In Kaplan-Meier analysis for disease-free interval, both 20% and 50% cut-off value of p53 expression had significant discriminating power for disease progression in both total population(p<0.05) and grade 2 subgroup (p<0.01). And 50% cut-off value showed higher confidence level. In conclusion, patients arfecred with T1 bladder cancers exhibiling nuclear overexpression of p53 protein have a higher probability of disease progression with short progression free interval and identirication of p53 nuclear overexpression in tumor cells may be useful in selecting appropriate therapy in T1 bladder cancer from TUR-B, BCG therapy to cystectomy.