title: Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma.
abstract: Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Brankley
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Halling
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Jenkins
authors.affiliation: Department of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Timmer
authors.affiliation: Department of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Iyer
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Smyrk
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: E G
authors.initials: EG
authors.lastname: Barr Fritcher
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Voss
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Kipp
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Campion
authors.affiliation: Department of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Lutzke
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Minot
authors.affiliation: Department of Gastroenterology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics*; D015342:DNA Probes; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004945:Esophagoscopy; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D015342:DNA Probes; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; C000614131:CDKN2A protein, human; C489427:MYC protein, human; C113698:ZNF217 protein, human; C508053:ERBB2 protein, human
keywords: Barrett's esophagus; FISH; cytology; esophageal adenocarcinoma; polysomy