Significance of p53 overexpression in urinary bladder transitional cell carcinoma in situ before and after bacillus Calmette-Guérin treatment

Abstract

Objectives. Overexpression of p53, normally secondary to gene mutation, in invasive uroepithelial neoplasms (transitional cell carcinoma) and a high percentage of transitional cell carcinoma in situ (CIS) has been described; however, the role of p53 before and after bacillus Calmette-Guérin (BCG) treatment of CIS needs to be defined. Methods. Immunohistochemical reaction for p53 overexpression was performed on 12 patients with CIS before and after BCG treatment. Thirty cystectomy specimens with invasive TCC were also evaluated for the presence of CIS, hyperplasia, and dysplasia. Results. Twenty-three cases of CIS were identified. Approximately 90% of CIS cases (21 of 23) were positive for p53 overexpression, whereas transitional cell hyperplasia was uniformly negative. Less than 5% of the cells in morphologically dysplastic lesions were positively stained. Ten of 12 CIS patients displayed p53 overexpression before BCG treatment. After BCG treatment, 4 patients displayed residual CIS with p53 overexpression, and 8 patients showed no residual CIS or p53 overexpression. Three of the 4 patients with residual CIS and overexpression rapidly developed invasive transitional cell carcinoma requiring cystectomy. The 1 remaining patient was treated with a second course of BCG; further biopsies displayed the development of grade 1 papillary transitional cell carcinoma without invasion, and the patient is currently being followed. Conclusions. Our data suggest that follow-up biopsy procedures are essential in all patients with CIS treated with BCG. The biopsy specimens should be evaluated for p53 overexpression, because our data indicate that persistent p53 overexpression in uroepithelial lesions after BCG treatment is an ominous finding for probable tumor progression.