SIGNIFICANCE OF P53 OVEREXPRESSION IN URINARY-BLADDER TRANSITIONAL-CELL CARCINOMA IN-SITU BEFORE AND AFTER BACILLUS-CALMETTE-GUERIN TREATMENT

Objectives, Overexpression of p53, normally secondary to gene mutation , in invasive uroepithelial neoplasms (transitional cell carcinoma) an d a high percentage of transitional cell carcinoma in situ (CIS) has b een described; however, the role of p53 before and after bacillus Calm ette-Guerin (BCG) treatment of CIS needs to be defined. Methods, Immun ohistochemical reaction for p53 overexpression was performed on 12 pat ients with CIS before and after BCG treatment, Thirty cystectomy speci mens with invasive TCC were also evaluated for the presence of CIS, hy perplasia, and dysplasia. Results, Twenty-three cases of CIS were iden tified, Approximately 90% of CIS cases (21 of 23) were positive for p5 3 overexpression, whereas transitional cell hyperplasia was uniformly negative. Less than 5% of the cells in morphologically dysplastic lesi ons were positively stained. Ten of 12 CIS patients displayed p53 over expression before BCC treatment. After BCG treatment, 4 patients displ ayed residual CIS with p53 overexpression, and 8 patients showed no re sidual CIS or p53 overexpression. Three of the 4 patients with residua l CIS and overexpression rapidly developed invasive transitional cell carcinoma requiring cystectomy. The 1 remaining patient was treated wi th 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 sugges t 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 overexp ression in uroepithelial lesions after BCC treatment is an ominous fin ding for probable tumor progression. (C) 1997, Elsevier Science Inc.