title: Role of Tetrasomy for the Diagnosis of Urothelial Carcinoma Using UroVysion Fluorescent In Situ Hybridization.
abstract: BACKGROUND
  -UroVysion fluorescent in situ hybridization (FISH) is routinely used to detect urothelial carcinoma (UC). A positive threshold is defined as chromosome polysomy in 4 or more cells, which also includes tetrasomy, a natural product of cell division.
  
  
  OBJECTIVE
  -To evaluate tetrasomy for UC detection and explore the relation to the surgical diagnosis or patient history.
  
  
  METHODS
  -The FISH was performed on 1532 urine samples from patients with cytology results and 4 or more years of follow-up. We created separate polysomy and tetrasomy categories and constructed receiver operating curves to determine appropriate thresholds using biopsy (n = 194) as the gold standard. Standard FISH and a novel assay integrating cytomorphology and FISH (Target-FISH) were compared. Matching tissue biopsies of urine samples with 10 or more tetrasomy cells were analyzed.
  
  
  RESULTS
  -No significant threshold was found for tetrasomy cells. Exclusion of tetrasomy from the polysomy category changed the threshold from 8.5 to 4.5 cells, increased specificity (59.2% to 78.9%), but reduced sensitivity (78.9% to 65.9%). In Target-FISH, the same approach yielded a specificity of 93.7% and sensitivity of 65.2%. Similarly, specificity improved significantly for low- and high-grade UC, but sensitivity decreased for low-grade UC. No evidence of UC was observed in 95% (52 of 55) of the patients referred for screening who had 10 or more tetrasomy cells by FISH. Matching biopsies for urines containing 10 or more tetrasomy cells showed few or no tetrasomy cells.
  
  
  CONCLUSIONS
  -Tetrasomy is a nonspecific finding frequently encountered in urine FISH and should be excluded from the polysomy classification. Target-FISH is an optimal approach, offering the ability to detect rare tetrasomy tumors.
authors.affiliation: From the Department of Pathology, University of Massachusetts Medical School, Worcester.
authors.forename: Amy G
authors.initials: AG
authors.lastname: Zhou
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Maryann St
authors.initials: MS
authors.lastname: Cyr
authors.forename: Joanne
authors.initials: J
authors.lastname: Garver
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Woda
authors.forename: Ediz F
authors.initials: EF
authors.lastname: Cosar
authors.forename: Lloyd M
authors.initials: LM
authors.lastname: Hutchinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D058670:Tetrasomy; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D019459:Urothelium / Q000473:pathology*