title: D-type cyclins in superficial and muscle-invasive bladder urothelial carcinoma: correlation with clinicopathological data and prognostic significance.
abstract: OBJECTIVE
  To elucidate the role of D-type cyclins in both superficial (Ta-T1) and muscle-invasive (T2-T4) urothelial carcinomas (UCs), investigating their potential prognostic usefulness.
  
  
  METHODS
  Paraffin-embedded tissues from 157 patients with bladder UC were immunostained for cyclins D1, D2 and D3.
  
  
  RESULTS
  Cyclin D1 expression positively correlated with D2 and negatively with D3. Cyclin D1 expression decreased with increasing grade (P = 0.0001) and tumour T-category in the entire cohort and in muscle-invasive carcinomas (P = 0.0001 and P = 0.0033). Cyclin D2 correlated with grade (P = 0.0005) and T-category (P = 0.0078), a relationship which remained significant in muscle-invasive (P = 0.0135). Cyclin D3 immunoreactivity increased with histologic grade and T-category in the entire cohort (P = 0.0001 in both relationships), in superficial (P = 0.0034) and in muscle-invasive carcinomas (P = 0.0036, respectively). Survival analysis in superficial tumours showed that higher cyclin D1 (P = 0.0001) and higher cyclin D3 levels (P = 0.0032) were correlated with a lesser probability of survival. In muscle-invasive tumours, lower cyclin D1 (P = 0.0234), and D2 (P = 0.0424) and higher cyclin D3 (P = 0.0322) correlated with shortened survival. In multivariate analysis in superficial tumours only cyclin D3 expression remained significant. Cyclin D3 expression also retained its adverse significance in muscle-invasive tumours.
  
  
  CONCLUSIONS
  Cyclin D1 overexpression seems to be more important during early T-categories of bladder carcinogenesis, whereas cyclin D3 is implicated in the acquisition of a more aggressive phenotype. Cyclin D3 overexpression emerges as an independent adverse prognostic marker in both superficial and muscle-invasive tumours. Cyclin D1 is an independent indicator of shortened survival only in muscle-invasive tumours.
authors.affiliation: First Department of Pathology, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece. glevidou@yahoo.gr
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
authors.forename: Maria
authors.initials: M
authors.lastname: Karlou
authors.forename: Irene
authors.initials: I
authors.lastname: Thymara
authors.forename: Harris
authors.initials: H
authors.lastname: Pratsinis
authors.forename: Petros
authors.initials: P
authors.lastname: Pavlopoulos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Isaiadis
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Diamantopoulou
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056741:Cyclin D / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology*
chemical_list: D056741:Cyclin D