title: PTEN deletions are related to disease progression and unfavourable prognosis in early bladder cancer.
abstract: OBJECTIVE
  This study aimed to determine the prevalence and clinical significance of deletions of the tumour suppressor gene PTEN in bladder cancer.
  
  
  RESULTS
  A tissue microarray with 686 bladder cancers was analysed for PTEN deletions by fluorescence in-situ hybridization. PTEN mutations were analysed in nine tumours with heterozygous PTEN deletion. Heterozygous PTEN deletions were present in 16.5% of tumours and were associated with grade (P = 0.0024) and p53 status (P = 0.0141), but not linked to stage (P = 0.0965). PTEN deletions were seen in 5.8% of pTaG1, 10.9% of pTaG2, 29.0% of pTaG3, 16.7% of pT1G2, 22.2% of pT1G3, 17.7% of pT2-4G2 and 20.9% of pT2-4G3 tumours (P = 0.0235). PTEN deletions were associated significantly with recurrences in pTa tumours (P = 0.0173), progression in pT1 tumours (P = 0.0016), but not with overall or cancer-specific survival in pT2 tumours. Multivariate analyses including grade and PTEN deletions revealed that PTEN deletions but not grade were associated independently with recurrence in pTa tumours (P = 0.0377) and progression in pT1 tumours (P = 0.0030). No inactivating PTEN mutations were found.
  
  
  CONCLUSIONS
  PTEN is linked to aggressive tumour phenotype and to unfavourable outcome in early bladder cancer. Heterozygous PTEN loss, i.e. reduced PTEN gene dosage, might be sufficient to cause aggressive tumour behaviour in bladder cancer cells.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Cordes
authors.forename: Martina
authors.initials: M
authors.lastname: Kluth
authors.forename: Dominika
authors.initials: D
authors.lastname: Zygis
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.forename: Felix
authors.initials: F
authors.lastname: Chun
authors.forename: Christian
authors.initials: C
authors.lastname: Eichelberg
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: Ousman
authors.initials: O
authors.lastname: Doh
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051059:PTEN Phosphohydrolase
keywords: PTEN; bladder cancer; tissue microarray