title: Prediction of response to endoscopic therapy of Barrett's dysplasia by using genetic biomarkers.
abstract: BACKGROUND
  Endoscopic therapy for the treatment of high-grade dysplasia (HGD) and intramucosal cancer (IMC) in Barrett's esophagus (BE) may not always result in complete remission of dysplasia (CRD).
  
  
  OBJECTIVE
  To determine whether genetic alterations in the Barrett's mucosa can predict response to endoscopic therapy.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Tertiary-care institution.
  
  
  METHODS
  Selected patients who underwent endoscopic therapy for BE containing HGD/IMC between 2003 and 2010.
  
  
  METHODS
  Endoscopic therapy combining mucosal resection and different ablation modalities was performed based on patient characteristics, endoscopic findings, and technique evolution. Fluorescence in situ hybridization was used to evaluate genetic alterations on baseline endoscopic cytology brushings by using probes directed to loci 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2; alias Her-2/neu), and 20q13.2 (ZNF217).
  
  
  METHODS
  Genetic biomarkers predicting achievement of CRD after endoscopic therapy.
  
  
  RESULTS
  A total of 181 patients were included (145 men; 66 ± 10 years of age). There were 130 patients (72%) who responded to endoscopic therapy with CRD. Multiple gains detected by fluorescence in situ hybridization was found to be a negative predictor (hazard ratio 0.57; 95% confidence interval, 0.40-0.82) after adjusting for potential clinical confounders. Similar results were found when analyses were restricted to patients (n = 66) undergoing radiofrequency ablation (hazard ratio 0.58; 95% confidence interval, 0.31-1.09).
  
  
  CONCLUSIONS
  Retrospective study, heterogeneity of treatment modalities.
  
  
  CONCLUSIONS
  Patients with multiple gains detected by brush cytology specimens may have a lower response rate to endoscopic therapy. The presence of multiple gains can be an adjunct to standard histology in prognosticating BE patients with HGD/IMC undergoing endoscopic therapy.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA; Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Margriet R
authors.initials: MR
authors.lastname: Timmer
authors.affiliation: Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Brankley
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Emmanuel C
authors.initials: EC
authors.lastname: Gorospe
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Lori S
authors.initials: LS
authors.lastname: Lutzke
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Prasad G
authors.initials: PG
authors.lastname: Iyer
authors.affiliation: Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Halling
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Kausilia K
authors.initials: KK
authors.lastname: Krishnadath
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics / Q000601:surgery*; D017115:Catheter Ablation; D015331:Cohort Studies; D004947:Esophagus / Q000601:surgery*; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D019942:Genes, p16; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000601:surgery*; D011379:Prognosis; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D015534:Trans-Activators / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D015534:Trans-Activators; C113698:ZNF217 protein, human
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