title: Copy number aberrations using multicolour fluorescence in situ hybridization (FISH) for prognostication in non-muscle-invasive bladder cancer (NIMBC).
abstract: OBJECTIVE
  To investigate if detection of copy number aberrations of chromosomes 3, 7, 9p21, and 17 using multicolour fluorescence in situ hybridization (FISH) predicts patient outcome in non-muscle-invasive bladder cancer (NMIBC).
  
  
  METHODS
  In all, 118 bladder wash samples were prospectively collected from patients who underwent transurethral resection of bladder tumour (median age 50.5 years, male/female: 91/27, tumour grade 1/2/3: 18/52/42, stage pTis/Ta/T1: 8/62/42) from 2007 to 2010. The 118 samples were analysed using the UroVysion® kit to detect the copy numbers of chromosomes 3, 7, 9p21, and 17. The variant fraction (VF; the sum of the non-modal copy number fraction of each chromosome) was defined as abnormal when the percentage was ≥16%. The percentage deletion of 9p21 (fraction of null or one copy number of the 9p21 locus) was defined as abnormal when the percentage was ≥12%. Maffezzini risk criteria were also analysed in our cohorts.
  
  
  RESULTS
  There was recurrence in 57 (48.3%) patients and disease progression in 12 (10.1%), with a median follow-up of 35.7 months. Multivariate analysis showed that the percentage 9p21 loss (>12%) was an independent prognostic factor for recurrence (P < 0.001, odds ratio [OR] 3.24, 95% confidence interval [CI] 1.85-5.62). For disease progression, tumour grade, positive urine cytology, concurrent carcinoma in situ, and a mean VF of >16% were significant prognostic factors in univariate analysis. In multivariate analysis, a mean VF of >16% was a prognostic factor for disease progression (P = 0.048, OR 6.07, 95% CI 1.02-57.45).
  
  
  CONCLUSIONS
  Multicolour-FISH analysis using a commercially available kit could be a powerful tool not only for diagnosis, but also for prognostication in patients with NMIBC.
authors.affiliation: Department of Urology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi-ken, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
authors.forename: Kenzo
authors.initials: K
authors.lastname: Ikemoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Eguchi
authors.forename: Atsunori
authors.initials: A
authors.lastname: Oga
authors.forename: Shigeto
authors.initials: S
authors.lastname: Kawauchi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kawai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagao
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakano
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics*; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics*; D018450:Disease Progression; D055088:Early Detection of Cancer; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D005819:Genetic Markers
keywords: 9p21; FISH; UroVysion; non-muscle-invasive bladder cancer; prognosis; variant fraction