title: Detection of circulating tumor cells in metastatic and clinically localized urothelial carcinoma.
abstract: OBJECTIVE
  To examine the incidence and prognostic value of circulating tumor cells (CTCs) in urothelial cancer (UC). The detection of CTCs is prognostic in several cancer types.
  
  
  METHODS
  A total of 44 subjects with UC were assessed for CTCs using CellSearch Technology and 7.5 mL of peripheral blood, sorted by magnetic separation (epithelial cell adhesion molecule positive) and immunofluorescent staining (positive for cytokeratin 8, 18, or 19, negative for CD45, positive for 4',6-diamidino-2-phenylindole) to identify the CTCs.
  
  
  RESULTS
  Five (17%) of 30 subjects with clinically localized and 7 (50%) of 14 subjects with metastatic UC had ≥1 detectable CTC (range 1-177). Six subjects had ≥5 CTCs. Fluorescence in situ hybridization analysis was performed in 20 samples from 18 unique subjects using the UroVysion probe set. Copy number gains consistent with neoplasm were observed in those with measurable CTCs but not in any of the CTC-negative samples tested. With a median follow-up of 337 days, all 7 patients with metastasis and detectable CTCs had died compared with 3 (43%) of the 7 with metastasis but without detectable CTCs.
  
  
  CONCLUSIONS
  CTCs are commonly observed in metastatic UC. CTCs were observed in 50% of the patients with metastatic UC tested. Fluorescence in situ hybridization analysis confirmed the aneusomic chromosomal content in the CTCs. These findings suggest that measurable CTCs might be prognostic for shortened survival in patients with metastatic UC, although the optimal threshold for a "positive" finding is unknown. CTCs were also detected in a subset of patients with clinically localized disease, identifying a potential high-risk, preoperative group for future study.
authors.affiliation: Department of Medicine, University of Colorado, School of Medicine, Aurora, CO, USA. Thomas.Flaig@ucdenver.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Flaig
authors.forename: Shandra
authors.initials: S
authors.lastname: Wilson
authors.forename: Adrie
authors.initials: A
authors.lastname: van Bokhoven
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: Pamela
authors.initials: P
authors.lastname: Wolfe
authors.forename: Paul
authors.initials: P
authors.lastname: Maroni
authors.forename: E Erin
authors.initials: EE
authors.lastname: Genova
authors.forename: Diana
authors.initials: D
authors.lastname: Morales
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000473:pathology*; D002469:Cell Separation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008856:Microscopy, Fluorescence / Q000379:methods; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012306:Risk; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*