Document Detail

Cyclin D3 expression in primary Ta/T1 bladder cancer.
MedLine Citation:
PMID:  16482499     Owner:  NLM     Status:  MEDLINE    
Cyclin D3 deregulation has recently been reported in bladder cancer but its prognostic significance remains uncertain. A cohort of 159 patients with stage Ta or T1 primary bladder tumours was investigated to determine the significance of cyclin D3 expression in association with other G1-S phase regulators of the cell cycle (p53, p21Waf1, p27kip1, cyclin D1), including tumour proliferation (ki67-MIB1); its association with conventional clinicopathological parameters; and the relationship between cyclin D3 and loss of heterozygosity (LOH) at the 9p21 (p16INK4a locus) chromosome region. The end point of the study was progression-free survival. Cyclin D3, other G1-S phase regulators, and tumour proliferation were investigated by immunohistochemistry and measured by the grid-counting method. To validate the immunohistochemical expression, cyclin D3 was additionally assessed by western blotting in selected cases. LOH at the 9p21 chromosome region (marker D9S171) was assessed in 125 cases using an AB Prism 310 genetic analyser and a set of microsatellite fluorescence-labelled primers. Cyclin D3 overexpression was related to larger tumour size (>5 cm; p < 0.0001) and high tumour proliferation (>10%; p = 0.025). Mean cyclin D3 expression increased with 2004 WHO grading categories in stage Ta (p = 0.035, ANOVA) and stage T1 (p = 0.047, t test) tumours. Cyclin D3 was not related to other clinicopathological parameters, G1-S phase modulators, or 9p21 LOH. Cox's multivariate analysis selected cyclin D3 as an independent predictor of progression-free survival (p = 0.0012, relative risk (RR) = 5.2366) together with tumour size (p = 0.0115, RR = 4.4442) and cyclin D1 (p = 0.0065, RR = 3.3023). Cyclin D3 expression had the highest risk ratio. Our results suggest that expression of cyclin D3 is relevant to the progression-free survival of patients with Ta/T1 bladder carcinomas.
A Lopez-Beltran; M J Requena; R J Luque; J Alvarez-Kindelan; A Quintero; A M Blanca; M E Rodriguez; E Siendones; R Montironi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pathology     Volume:  209     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-10     Completed Date:  2006-06-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  106-13     Citation Subset:  IM    
Copyright Information:
Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Department of Pathology, Reina Sofia University Hospital and Cordoba University Medical School, Spain.
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MeSH Terms
Aged, 80 and over
Blotting, Western
Cell Cycle
Cell Differentiation
Chromosomes, Human, Pair 9 / genetics
Cyclin D3
Cyclins / metabolism*
Disease-Free Survival
Immunoenzyme Techniques
Loss of Heterozygosity
Middle Aged
Neoplasm Proteins / metabolism
Proportional Hazards Models
Tumor Markers, Biological / metabolism*
Urinary Bladder Neoplasms / genetics,  metabolism*,  pathology
Reg. No./Substance:
0/CCND3 protein, human; 0/Cyclin D3; 0/Cyclins; 0/Neoplasm Proteins; 0/Tumor Markers, Biological

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