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Prognostic Factors in Survival of Patients With Stage Ta and T1 Bladder Urothelial Tumors
The Role of G1-S Modulators (p53, p21Waf1, p27Kip1, Cyclin D1, and Cyclin D3), Proliferation Index, and Clinicopathologic Parameters

Antonio Lopez-Beltran MD, PhD, Rafael J. Luque MD, PhD, Jose Alvarez-Kindelan MD, Ana Quintero PhD, Felix Merlo MD, Maria J. Requena MD, Rodolfo Montironi MD, FRCPath
DOI: http://dx.doi.org/10.1309/LTFU3UUMBY095HUM 444-452 First published online: 1 September 2004


We studied 159 cases of superficial (stage Ta or T1) bladder tumors to determine the significance on survival of a subset of regulators of transition from G1 to S phase of the cell cycle (p53, p21Waf1, p27Kip1, cyclin D1, cyclin D3) and tumor proliferation (Ki-67 [MIB-1]). Clinical findings (patient age, sex, tumor size, grade, stage [Ta or T1]) were included in the analysis. Univariate analysis revealed association of tumor size (P = .0353), grade in stage Ta tumors ( P = .0074), cyclin D1 expression (P = .0182), and Ki-67 index ( P = .0033) with disease-free survival and of tumor size ( P = .0005), stage (P = .0494), cyclin D3 expression ( P = .0105), and Ki-67 index ( P = .0272) with overall survival. Cox multivariate analysis revealed cyclin D1 expression and high proliferation index (disease-free) and tumor size, cyclin D3 expression, and high proliferation index (overall survival) as independent predictors. Results suggest that alterations of the progression from the G1 to S phase of the cell cycle are common in papillary urothelial bladder tumors. High tumor proliferation, expression of cyclins D1 and D3, and tumor size at diagnosis might be relevant predictors of survival in patients with stage Ta and T1 bladder urothelial tumors.

Key Words:
  • Bladder cancer
  • Survival
  • Cyclin D3
  • Cyclin D1
  • Tumor size
  • Ki-67
  • Grade
  • p21Waf1
  • p27Kip1
  • p53