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 urinary tract is based mainly on histologic grade and stage of the tumors. In recent years, tumor proliferation has also proved to be an important factor in determining the prognosis of these and other transitional cell tumors. The aim of this study was to assess the role of p53 in regulating cell proliferation and tumor progression and to define its value in predicting the long term survival of patients with these tumors. Such information could be of use in selecting treatment in individual cases. METHODS. Eighty-three patients with urothelial tumors of the renal pelvis and ureter diagnosed and treated between 1975 and 1993 were included in this study, p53 immunostaining was performed on paraffin embedded tissue. Tumor location, histologic grade, histologic pattern, tumor proliferation bg Ki-67, local (T classification), lymph node (N classification), vascular and perineural invasion, and clinical stage (TNM) were assessed in relation to p53 overexpression (Man-Whitney U test and analysis of variance comparisons) and as prognostic factors for survival in both univariate analysis (log rank test) and multivariate analysis (Cox proportional hazards model). RESULTS. Overexpression 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 also a statistically significant relation to vascular (P < 0.002) and perineural invasion (P < 0.04). Fifteen-year actuarial survival for the whole group was 75%. Patients having tumors with low p53 overexpression (< 30% of stained nuclei) had a better survival rate (88%) than those 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, patients 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 significant. CONCLUSIONS. Overexpression of p53 is related to increased tumor proliferation and disease progression and is of value in determining the long term survival of patients with tumors of the renal pelvis 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 for survival. (C) 1997 American Cancer Society.