title: Y chromosome loss is a frequent early event in urothelial bladder cancer.
abstract: OBJECTIVE
  Y chromosome losses have been described in 10-40% of bladder cancers and were suggested to be age-related. The clinical significance of chromosome Y losses is largely unknown, since only small sets of male bladder cancer patients have been evaluated in previous studies. The aim of this study was to further clarify the potential relevance of Y chromosome losses in bladder cancer with respect to clinical outcome and patient age.
  
  
  METHODS
  A pre-existing bladder cancer tissue microarray (TMA) with clinical follow-up data including 516 urothelial bladder cancers from male patients was utilised in this study. Y chromosome losses were analysed by multicolour fluorescence in situ hybridisation (FISH) using a centromere Y probe and a centromere X probe. p53 immunostaining data were available for all patients from a previous study.
  
  
  RESULTS
  Y chromosome losses were seen in 23% of 477 interpretable cancers from male patients. There was no significant difference in patient age in tumours with (67.4 +/- 4.3 years) or without (67.3 +/- 2.3 years) Y chromosome losses (p = 0.9068). Y chromosome losses were equally frequent in tumours of all grades (p = 0.7831) and stages (p = 0.6140). There was also no association with p53 immunostaining (p = 0.4092). Y chromosome losses were not associated with survival in 224 invasive urothelial cancers (pT2-4; p = 0.2324), an increased risk for recurrences in 197 pTa tumours (p = 0.7649) or increased progression risk in 76 pT1 tumours (p = 0.4582).
  
  
  CONCLUSIONS
  The data of this study show that Y chromosome losses are frequent in urothelial bladder cancer of all grades and stages, which could imply that loss of the Y chromosome is an early event in bladder cancer development. p53 mediated genomic instability is evidently not required for the development of Y chromosome losses. Since there was no correlation between Y chromosome losses and clinical outcome, detection of Y losses has no clinical relevance in urothelial bladder cancer.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany. s.minner@uke.uni-hamburg.de
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Adisa
authors.initials: A
authors.lastname: Kilgué
authors.forename: Phillip
authors.initials: P
authors.lastname: Stahl
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.forename: Roland
authors.initials: R
authors.lastname: Dahlem
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Höppner
authors.forename: Walter
authors.initials: W
authors.lastname: Wagner
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
mesh_terms: D000367:Age Factors; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000473:pathology