Significance of p53 and P-glycoprotein Expression and its Relationship in Bladder Cancer

Chung, Jong Kap; Park, Dong Soo; Oh, Kil Hyun

Abstract

Overexpression of the MDR1 gene product, P-glycoprotein (Pgp), has been shown to be one of the mechanism underlying the development of mutidrug resistance in bladder cancer. Recently, mutant p53 has been shown to stimulate the P-glycoprotein and to being strongly associated with tumor progression and malignant biological behavior, whereas wild-type p53 repressed this activity. To evaluate the correlation of p53 expression with P-glycoprotein, to study expression pattern of two parameters according to histologic grade, tumor stage and recurrence, we examined expression of p53 and Pgp in paraffin-embedded tissues from 59 transitional cell carcinoma of bladder. Expressions of p53 and Pgp Protein were detected by immunohistochemical analysis using the monoclonal antibody BP53.12 and JSB-1. Among the cases of 59 patients, 36 were from patients of superficial bladder cancer, 23 were from invasive bladder cancer. Median follow-up duration was 31.8 months (1~55 months). The results were as follow: 1. p53 was detected in 34% (20/59), and Pgp in 42% (25/59) of the bladder cancer. 2. Eight out of the 20 specimens with p53 positive stain expressed positive Pgp expression, as compared to 17 out of the 39 specimens without p53 positive stain. This result showed that Pgp expression was not associated with p53 expression (p=0.98), suggesting that mutant p53 does not induce Pgp expression in bladder cancer. 3. Seven of 12 patients with p53 positive stain revealed tumor recurrence, whereas 2 of 24 patients without p53 positive stain showed recurrence in superficial bladder cancer. There ia s significant correlation between p53 expression and recurrence (p=0.0025). 4. Expression of p53 and Pgp showed enhanced positive tendency according to higher clinicopathological stage, but difference was not statistically significant. Also positivity of Pgp expression according to histologic grade was observed significantly higher in case with high grade tumors (14/25, 56%) than in case with low grade tumors (10/34, 29%) (p=0.03). These results show that superficial bladder cancers exhibiting expression of p53 protein are associated with a higher rate of recurrence. This study also suggests that Pgp expression is significantly more common in higher grade, and mutant p53 does not induce Pgp expression in bladder cancer.