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Prognostic factors in stage T1 grade 3 bladder cancer survival: the role of G1-S modulators (p53, p21Waf1, p27kip1, Cyclin D1, and Cyclin D3) and proliferation index (ki67-MIB1).
Eur Urol. 2004 May; 45(5):606-12.EU

Abstract

OBJECTIVE

To determine the prognostic value of a subset of regulators of the transition from G1-to-S phase of cell cycle in stage T1 grade 3 bladder cancers.

METHODS

Fifty-one such cases were investigated to determine the significance on patient's survival of p53, p21Waf1, p27Kip1, Cyclin D1, Cyclin D3, and ki67-MIB1 (proliferation index). The statistical analysis included Kaplan-Meier methodology with Log-rank test and Cox' proportional hazard analysis.

RESULTS

Tumor size (p=0.0034), and the labeling index of ki67-MIB1 (p=0.0034), p53 (p=0.0332), p27kip1 (p=0.0059) and Cyclin D1 (p=0.0103) were associated to disease-free survival. Progression-free survival was related to tumor size (p<0.0001), ki67 (p=0.0163), p53 (p=0.0041), p27kip1 (p=0.0161), Cyclin D1 (p<0.0001) and Cyclin D3 (p<0.0001). Patient's overall survival was associated to Cyclin D3 (p<0.0001), p53 (p=0.0017), p21Waf1 (p=0.0142), Cyclin D1 (p<0.0001), ki67-MIB1 (p=0.0450), and tumor size (p=0.0296). Down-regulation of p27kip1 and Cyclin D3 over-expression (disease-free), over-expression of p53, Cyclin D1 and Cyclin D3 (progression-free), and over-expression of Cyclin D3 (overall survival) were independent predictors by Cox's multivariate analysis. Down-regulation of p27kip1 (p<0.001, R.R. 0.997, 95%C.I. 0.995-0.999), and over-expression of Cyclin D1 (p<0.001, R.R. 1.009, 95%C.I. 1.004-1.014) and Cyclin D3 (p=0.005, R.R. 1.013, 95%C.I. 1.004-1.022) were the main independent predictors.

CONCLUSION

Down-regulation of p27kip1 and over-expression of Cyclin D1 and Cyclin D3 might be relevant predictors of survival in stage T1 grade 3 bladder cancers, thus selecting a group of patients at higher risk of malignant behavior.

Authors+Show Affiliations

Department of Pathology, Reina Sofia University Hospital and Cordoba University Medical School, Cordoba, Spain. em1lobea@uco.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15082203

Citation

Lopez-Beltran, A, et al. "Prognostic Factors in Stage T1 Grade 3 Bladder Cancer Survival: the Role of G1-S Modulators (p53, p21Waf1, P27kip1, Cyclin D1, and Cyclin D3) and Proliferation Index (ki67-MIB1)." European Urology, vol. 45, no. 5, 2004, pp. 606-12.
Lopez-Beltran A, Luque RJ, Alvarez-Kindelan J, et al. Prognostic factors in stage T1 grade 3 bladder cancer survival: the role of G1-S modulators (p53, p21Waf1, p27kip1, Cyclin D1, and Cyclin D3) and proliferation index (ki67-MIB1). Eur Urol. 2004;45(5):606-12.
Lopez-Beltran, A., Luque, R. J., Alvarez-Kindelan, J., Quintero, A., Merlo, F., Carrasco, J. C., Requena, M. J., & Montironi, R. (2004). Prognostic factors in stage T1 grade 3 bladder cancer survival: the role of G1-S modulators (p53, p21Waf1, p27kip1, Cyclin D1, and Cyclin D3) and proliferation index (ki67-MIB1). European Urology, 45(5), 606-12.
Lopez-Beltran A, et al. Prognostic Factors in Stage T1 Grade 3 Bladder Cancer Survival: the Role of G1-S Modulators (p53, p21Waf1, P27kip1, Cyclin D1, and Cyclin D3) and Proliferation Index (ki67-MIB1). Eur Urol. 2004;45(5):606-12. PubMed PMID: 15082203.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prognostic factors in stage T1 grade 3 bladder cancer survival: the role of G1-S modulators (p53, p21Waf1, p27kip1, Cyclin D1, and Cyclin D3) and proliferation index (ki67-MIB1). AU - Lopez-Beltran,A, AU - Luque,R J, AU - Alvarez-Kindelan,J, AU - Quintero,A, AU - Merlo,F, AU - Carrasco,J C, AU - Requena,M J, AU - Montironi,R, PY - 2003/11/14/accepted PY - 2004/4/15/pubmed PY - 2004/8/31/medline PY - 2004/4/15/entrez SP - 606 EP - 12 JF - European urology JO - Eur. Urol. VL - 45 IS - 5 N2 - OBJECTIVE: To determine the prognostic value of a subset of regulators of the transition from G1-to-S phase of cell cycle in stage T1 grade 3 bladder cancers. METHODS: Fifty-one such cases were investigated to determine the significance on patient's survival of p53, p21Waf1, p27Kip1, Cyclin D1, Cyclin D3, and ki67-MIB1 (proliferation index). The statistical analysis included Kaplan-Meier methodology with Log-rank test and Cox' proportional hazard analysis. RESULTS: Tumor size (p=0.0034), and the labeling index of ki67-MIB1 (p=0.0034), p53 (p=0.0332), p27kip1 (p=0.0059) and Cyclin D1 (p=0.0103) were associated to disease-free survival. Progression-free survival was related to tumor size (p<0.0001), ki67 (p=0.0163), p53 (p=0.0041), p27kip1 (p=0.0161), Cyclin D1 (p<0.0001) and Cyclin D3 (p<0.0001). Patient's overall survival was associated to Cyclin D3 (p<0.0001), p53 (p=0.0017), p21Waf1 (p=0.0142), Cyclin D1 (p<0.0001), ki67-MIB1 (p=0.0450), and tumor size (p=0.0296). Down-regulation of p27kip1 and Cyclin D3 over-expression (disease-free), over-expression of p53, Cyclin D1 and Cyclin D3 (progression-free), and over-expression of Cyclin D3 (overall survival) were independent predictors by Cox's multivariate analysis. Down-regulation of p27kip1 (p<0.001, R.R. 0.997, 95%C.I. 0.995-0.999), and over-expression of Cyclin D1 (p<0.001, R.R. 1.009, 95%C.I. 1.004-1.014) and Cyclin D3 (p=0.005, R.R. 1.013, 95%C.I. 1.004-1.022) were the main independent predictors. CONCLUSION: Down-regulation of p27kip1 and over-expression of Cyclin D1 and Cyclin D3 might be relevant predictors of survival in stage T1 grade 3 bladder cancers, thus selecting a group of patients at higher risk of malignant behavior. SN - 0302-2838 UR - https://www.unboundmedicine.com/medline/citation/15082203/Prognostic_factors_in_stage_T1_grade_3_bladder_cancer_survival:_the_role_of_G1_S_modulators__p53_p21Waf1_p27kip1_Cyclin_D1_and_Cyclin_D3__and_proliferation_index__ki67_MIB1__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0302283803005888 DB - PRIME DP - Unbound Medicine ER -