Expression of p53 Protein and its Clinical Significance in Transitional Cell Carcinoma of the Urinary Bladder

Choi, Do Yeoun; Woo, Young Nam

Abstract

To evaluate the prevalence and the role of mutation of p53 gene in the transitional ceI1 carcinoma of the urinary bladder with special attention to the clinicopathologic features, we examined p53 expression in paraffin-embedded tissues from 95 transitional cell carcinomas with various stages and grades and 5 specimens of morphologically normal bladder. Nuclear expression of p53 protein was detected by immunohistochemical analysis with avidin -alkaline phosphatase method, using the monoclonal antibody DO-7. And to evaluate the correlation of p53 expression with cell proliferation, expression of proliferating cell nuclear antigen(PCNA) was also assessed immunohistochemically in 43 specimens, using the monoclonal antibody PC1O. Median follow-up duration was 36 months(12-117 months). Immunohistochemical staining with p53 in 5 normal bladder specimens showed that 4 specimens exhibited absence of nuclear staining in urothelial and stromal cells and 1 specimen exhibited nuclear staining less than 5% of urothelial cells in the basal layer. Forty six(48%) of 95 specimens with transitional cell carcinoma of the bladder showed positive nuclear staining. Nuclear expression of p53 was observed with significantly higher frequency and stronger intensity(p<0.01 and p<0.005, respectively) in cases with invasive tumors(17,27, 70%) than superficial tumors(27/68, 40%). Nuclear expression of p53 was observed with signi6cantly higher frequency and stronger intensity(p<0.005 and p<0.005, respectively) in. cases with high grade tumors(32,43, 74%) than in cases with low grade tumors(14/52, 27%). Patients with bladder tumors were stratified into two groups with different patterns of staining for p53 protein (group A: <20%, group B: >20%). Recurrence rates of patients with superficial tumors were 2.2% per month for group A and 4.2% for group B, and patients in group B had a significantly 1ower disease-free interval(P<0.005). Disease progression rates of patients with T1 tumors were 4% per year and 21.2% for group B, and patients in group B had a significantly lower progression- free interval(P<0.025). Difference of survivorship of patients with invasive tumors between group A and B was not statistically significant(p>O.1). Mean value of PCNA expression rates of 43 transitional cell carcinomas of the bladder was 12.1+8.34%(mean + SD). Mean value of PCNA expression rates was slightly higher in p53 positive-stained group(13.2+/-7.81%) than negative stained group(10.8+/-8.89%), but difference was not statistically significant(p>0.1). These results suggest that p53 mutations play an important role in the acquisition of aggressive biological natures in invasive bladder transitional cell carcinomas rather than in the genesis of tumors of low malignant potentials. This study also suggests that immunohistochemical examination of p53 in superficial bladder transitional cell carcinomas (especially, T1 tumors) offers significant information, and the degree of p53 expression might be a useful prognostic indicator which can be considered in treatment planning.