OVEREXPRESSION OF P53 IN TRANSITIONAL-CELL CARCINOMA OF THE RENAL PELVIS AND URETER - RELATION OF TUMOR PROLIFERATION AND SURVIVAL

BACKGROUND. Clinical management of patients with tumors of the upper u rinary tract is based mainly on histologic grade and stage of the tumo rs. In recent years, tumor proliferation has also proved to be an impo rtant factor in determining the prognosis of these and other transitio nal cell tumors. The aim of this study was to assess the role of p53 i n regulating cell proliferation and tumor progression and to define it s value in predicting the long term survival of patients with these tu mors. Such information could be of use in selecting treatment in indiv idual cases. METHODS. Eighty-three patients with urothelial tumors of the renal pelvis and ureter diagnosed and treated between 1975 and 199 3 were included in this study, p53 immunostaining was performed on par affin embedded tissue. Tumor location, histologic grade, histologic pa ttern, tumor proliferation bg Ki-67, local (T classification), lymph n ode (N classification), vascular and perineural invasion, and clinical stage (TNM) were assessed in relation to p53 overexpression (Man-Whit ney U test and analysis of variance comparisons) and as prognostic fac tors for survival in both univariate analysis (log rank test) and mult ivariate analysis (Cox proportional hazards model). RESULTS. Overexpre ssion of p53 was related to tumor proliferation as assessed by Ki-67 [ P < 0.01), T classification (Ta vs. T1-4; P < 0.01), N classification (P < 0.054), and TNM staging (Stage 0 vs. I-IV; P < 0.01]. There was a lso a statistically significant relation to vascular (P < 0.002) and p erineural invasion (P < 0.04). Fifteen-year actuarial survival for the whole group was 75%. Patients having tumors with low p53 overexpressi on (< 30% of stained nuclei) had a better survival rate (88%) than tho se having tumors with high (> 30%) p53 overexpression (65%) (P < 0.02) , and this effect reached statistical significance with high grade (P < 0.02) and infiltrating tumors (P < 0.04). Patients with low p53 and Ki-67 expression had a 15-year survival rate of 100%; in contrast, pat ients with overexpression of both markers had a 15-year survival rate of 61% (P < 0.003). In a multivariate analysis, only T classification (P < 0.001) and p53-Ki-67 expression (P < 0.026) were statisti cally s ignificant. CONCLUSIONS. Overexpression of p53 is related to increased tumor proliferation and disease progression and is of value in determ ining the long term survival of patients with tumors of the renal pelv is and ureter. p53 immunostaining can be used to distinguish low risk patients in the theoretically unfavorable high grade, high stage group , and when used together with Ki-67 index, it is a predictive factor f or survival. (C) 1997 American Cancer Society.