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Prognostic Factors in Survival of Patients With Stage Ta and T1 Bladder Urothelial Tumors The Role of G<SUB>1</SUB>-S Modulators (p53, P21Waf1, p27Kip1, Cyclin D1, and Cyclin D3), Proliferation Index and Clinicopathologic Parameters

Department of Pathology, Reina Sofia University Hospital, Cordoba, Spain.
American Journal of Clinical Pathology (Impact Factor: 3.01). 10/2004; 122(3):444-52. DOI: 10.1309/LTFU-3UUM-BY09-5HUM
Source: PubMed

ABSTRACT 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.

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    • "These patients could potentially benefit from early aggressive therapy. Ki-67 has been reported as a prognostic marker for disease and progression-free survival in pTa and pT1 UCC [18] [26]. In the 203 pTa and pT1 tumours across all grades investigated in this study, we were able to confirm its relation to disease progression ( p < 0.03). "
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    • "The results presented in this manuscript clearly demonstrate a correlation between p53 levels and cyclin D1 expression. To the best of our knowledge, this is one of the few reports, which directly correlates p53 status with cyclin D1 since both are regulators of G1 to S phase transition [31]. p53 overexpression downregulates Akt which is constitutively active in MCF-7As53 cells Akt activation which is downstream of PI3-K pathway is known to be involved in cell growth and survival [32]. "
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    • "Two well-established markers are CK20 (Harnden et al, 1999) and Ki67 (van Rhijn et al, 2003; Lopez-Beltran et al, 2004). Ki67 is a commonly applied prognostic and diagnostic tool (van Rhijn et al, 2003; Lopez-Beltran et al, 2004), as the Ki67 protein is present in the nuclei of cells in the G 1 , S, and G 2 phases of the cell cycle in dividing cells as well as in mitosis but not in the G 0 phase of quiescent cells. Nevertheless it is unlikely that Ki67 reliably labels the entire proliferative cell fraction. "
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