title: Prognostic value of cell cycle regulatory proteins in muscle-infiltrating bladder cancer.
abstract: OBJECTIVE
  The aims of this study were to investigate the expression levels of proteins involved in cell cycle regulation in specimens of bladder cancer and to correlate them with the clinicopathological characteristics, proliferative activity and survival.
  
  
  METHODS
  Eighty-two specimens obtained from patients affected by muscle-invasive bladder cancer were evaluated immunohistochemically for p53, p21 and cyclin D1 expression, as well as for the tumour proliferation index, Ki-67. The statistical analysis included Kaplan-Meier curves with log-rank test and Cox proportional hazards models.
  
  
  RESULTS
  In univariate analyses, low Ki-67 proliferation index (P = 0.045) and negative p21 immunoreactivity (P = 0.04) were associated to patient's overall survival (OS), but in multivariate models p21 did not reach statistical significance. When the combinations of the variables were assessed in two separate multivariate models that included tumour stage, grading, lymph node status, vascular invasion and perineural invasion, the combined variables p21/Ki-67 or p21/cyclin D1 expression were independent predictors for OS; in particular, patients with positive p21/high Ki-67 (P = 0.015) or positive p21/negative cyclin D1 (P = 0.04) showed the worst survival outcome.
  
  
  CONCLUSIONS
  Important alterations in the cell cycle regulatory pathways occur in muscle-invasive bladder cancer and the combined use of cell cycle regulators appears to provide significant prognostic information that could be used to select the patients most suitable for multimodal therapeutic approaches.
authors.affiliation: Department of Medical Oncology, University of Genova, Genova, Italy.
authors.forename: Fabia
authors.initials: F
authors.lastname: Galmozzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rubagotti
authors.forename: Andrea
authors.initials: A
authors.lastname: Romagnoli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Carmignani
authors.forename: Luisa
authors.initials: L
authors.lastname: Perdelli
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gatteschi
authors.forename: Francesco
authors.initials: F
authors.lastname: Boccardo
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D049109:Cell Proliferation; D015331:Cohort Studies; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D016213:Cyclins / Q000096:biosynthesis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53