title: A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett's Esophagus.
abstract: OBJECTIVE
  Preliminary single-institution data suggest that fluorescence in situ hybridization (FISH) may be useful for detecting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EA) in patients with Barrett's esophagus (BE). This multicenter study aims to validate the measurement of polysomy (gain of at least two loci) by FISH as a way to discriminate degrees of dysplasia in BE specimens.
  
  
  METHODS
  Tissue specimens were collected from four different hospitals and read by both the local pathology department ("Site diagnosis") and a single central pathologist ("Review diagnosis") at a separate institution. The specimens then underwent FISH analysis using probes 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) for comparison. A total of 46 non-BE, 42 non-dysplastic specialized intestinal metaplasia (SIM), 23 indefinite-grade dysplasia (IGD), 10 low-grade dysplasia (LGD), 29 HGD, and 42 EA specimens were analyzed.
  
  
  RESULTS
  We found that polysomy, as detected by FISH, was the predominant chromosomal abnormality present as dysplasia increased. Polysomy was also the best predictor for the presence of dysplasia or EA when comparing its area under the curve to that of other FISH abnormalities. We observed that if at least 10% of cells had polysomy within a specimen, the FISH probe was able to differentiate between EA/HGD and the remaining pathologies with a sensitivity of 80% and a specificity of 88%.
  
  
  CONCLUSIONS
  This study demonstrates that using FISH to determine the percentage of cells with polysomy can accurately and objectively aid in the diagnosis of HGD/EA in BE specimens.
authors.affiliation: Department of Gastroenterology, Columbia University Medical Center, 161 Fort Washington Avenue, Suite 862, New York, NY, 10032, USA. jmp14@cumc.columbia.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Poneros
authors.affiliation: Department of Internal Medicine, Columbia University Medical Center, 177 Fort Washington Avenue, Milstein 6C-12, New York, NY, 10032, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Faye
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First SW, Rochester, MN, 55905, USA.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Barr Fritcher
authors.affiliation: Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, MI, USA.|Department of Family Medicine, University of Michigan Medical School, 1018 Fuller St., Ann Arbor, MI, 48104, USA.
authors.forename: Ananda
authors.initials: A
authors.lastname: Sen
authors.affiliation: Department of Gastroenterology, Baylor College of Medicine, Baylor St. Luke's Medical Center Clinic, 7200 Cambridge Street Suite 10C, Houston, TX, 77030, USA.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Anandasabapathy
authors.affiliation: Department of Gastroenterology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1466, Houston, TX, 77030, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bresalier
authors.affiliation: Department of Gastroenterology, University of Toronto, Toronto, ON, Canada.|St. Michael's Hospital, University of Toronto, 30 Bond Street, 16-062 Cardinal Carter South Wing, Toronto, ON, M5B 1W8, Canada.
authors.forename: Norman
authors.initials: N
authors.lastname: Marcon
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.|Department of Gastroenterology, University of Michigan Health System, Taubman Center Floor 3, Reception D, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA.
authors.forename: D Kim
authors.initials: DK
authors.lastname: Turgeon
authors.affiliation: Department of Pathology, University of Michigan Medical Center, 1301 Catherine St., Ann Arbor, MI, 48109, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Appelman
authors.affiliation: Department of Biostatistics, University of Pittsburgh Cancer Institute, 201 North Craig Street, Sterling Plaza Suite 325, Pittsburgh, PA, 15213, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Normolle
authors.affiliation: Abbott Molecular, Inc., Des Plaines, IL, USA.|Ventana Medical Systems Inc., 1910 E. Innovation Park Dr., Tucson, AZ, 85755, USA.
authors.forename: Larry E
authors.initials: LE
authors.lastname: Morrison
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.|Department of Pharmacology, University of Michigan Medical Center, 1500 E Medical Center Dr #2150, Ann Arbor, MI, 48109, USA.
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First SW, Rochester, MN, 55905, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Halling
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D001471:Barrett Esophagus / Q000150:complications* / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D012372:ROC Curve; D012680:Sensitivity and Specificity
keywords: Barrett’s esophagus; Dysplasia; Endoscopy; FISH; Histopathology; Polysomy