title: Expression of the p53 Inhibitors MDM2 and MDM4 as Outcome Predictor in Muscle-invasive Bladder Cancer.
abstract: To evaluate the prognostic role of the p53-upstream inhibitors MDM2, MDM4 and its splice variant MDM4-S in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC).
  
  
  
  mRNA Expression levels of MDM2, MDM4 and MDM4-S were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) in 75 RC samples. Logistic regression analyses identified predictors of recurrence-free (RFS) and cancer-specific survival (CSS).
  
  
  
  High expression was found in 42% (MDM2), 27% (MDMD4) and 91% (MDM4-S) of tumor specimens. Increased MDM2 expression was significantly associated with higher tumor stage (p=0.05) and lymphovascular invasion (LVI) (p=0.041). In the univariate analysis, low MDM4 expression (hazard ratio (HR)=5.93; p=0.002; HR=3.00; p=0.047), but not MDM2 (HR=1.63; p=0.222; HR=1.59; p=0.27), were associated with RFS and CSS. In the multivariate analysis, the combination of low MDM4 and high MDM2 was significant for RFS and CSS (HR=14.9; p=0.001; HR=5.63; p=0.019).
  
  
  
  The combination of MDM2 and MDM4 expression is an independent predictor in patients undergoing RC for MIBC.
authors: Department of Urology, University Medical Centre Mannheim, Mannheim, Germany maximilian.kriegmair@medma.uni-heidelberg.de.
authors: Maximilian Christian
authors: MC
authors: Kriegmair
authors: Department of Urology, University Medical Centre Mannheim, Mannheim, Germany.
authors: Matthias
authors: M
authors: Balk
authors: Stratifyer Molecular Pathology, Köln, Germany.
authors: Ralph
authors: R
authors: Wirtz
authors: Department of Urology, University Medical Centre Mannheim, Mannheim, Germany.
authors: Annette
authors: A
authors: Steidler
authors: Institute of Pathology, University Medical Centre Mannheim, Mannheim, Germany.
authors: Cleo-Aron
authors: CA
authors: Weis
authors: Department of Urology, University of Regensburg, Regensburg, Germany.
authors: Johannes
authors: J
authors: Breyer
authors: Institute of Pathology, University Erlangen-Nuernberg, Erlangen, Germany.
authors: Arndt
authors: A
authors: Hartmann
authors: Department of Urology, University of Ulm, Ulm, Germany.
authors: Christian
authors: C
authors: Bolenz
authors: Department of Urology, University Medical Centre Mannheim, Mannheim, Germany.
authors: Philipp
authors: P
authors: Erben
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015653:Cystectomy; D005260:Female; D006801:Humans; D008297:Male; D019042:Muscle Neoplasms / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D009132:Muscles / Q000473:pathology; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: HDMX; MDM2; bladder cancer; marker; prognosis