P53 IMMUNOHISTOCHEMISTRY AS AM INDEPENDENT PROGNOSTIC FACTOR FOR SUPERFICIAL TRANSITIONAL-CELL CARCINOMA OF THE BLADDER

Although patients with superficial bladder cancer (Ta, Tl) have a gene rally good prognosis, those patients who develop muscle-invasive tumou rs or metastatic disease at recurrence do poorly clinically. In the cu rrent study 69 patients undergoing complete transurethral resection fo r superficial transitonal cell cancer of the bladder were investigated for different clinical and biological characteristics as possible pro gnostic factors: age, sex, performance of instillation therapy and imm unohistochemical determination of mutational inactivation of p53 tumou r-suppressor gene (monoclonal antibody PAb 1801) as well as immunohist ochemical determination of the proliferation rate by staining for PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). Aft er a median follow-up of 45.8 months, 12 of 14 patients (85.7%) with m ore than 20% of cells positive for p53 had disease progression with mu scle-invasive growth compared with only one of 55 patients (1.8%) nega tive for p53 (P <0.01, chi(2) test). During univariate analysis histol ogical grade (G(1) vs G(2)) (P = 0.0373), positivity for PCNA (>60% of cells) (P = 0.0033) and positivity for p53 (P <0.001) were significan t prognostic factors for disease progression (log-rank test), while du ring multivariate analysis only positivity for p53 was a significant p redictor for relapse of bladder cancer (P = 0.0029) (multivariate Cox regression analysis). The immunohistochemical detection of mutations o f the p53 gene has been demonstrated to be a reliable, easily performe d and thereby widely available technique for the investigation of fres h-frozen or paraffin-embedded tumour specimens. The results demonstrat e the important role of the p53 tumour-suppressor gene protein in the development and for the progression of bladder cancer. If the high pro gnostic value of p53 mutations in superficial bladder cancer is confir med in larger prospective trials, more aggressive therapeutic strategi es could be discussed for patients with p53 mutations in their tumour specimens.