title: A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus.
abstract: There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC.
  
  
  
  We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days).
  
  
  
  The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis.
  
  
  
  A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test.
  
  
  
  A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR.
authors.affiliation: Cernostics, Inc., Pittsburgh, Pennsylvania. rthorne@cernostics.com.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Critchley-Thorne
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Davison
authors.affiliation: Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Prichard
authors.affiliation: Cernostics, Inc., Pittsburgh, Pennsylvania.
authors.forename: Lia M
authors.initials: LM
authors.lastname: Reese
authors.affiliation: Cernostics, Inc., Pittsburgh, Pennsylvania.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cernostics, Inc., Pittsburgh, Pennsylvania.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Repa
authors.affiliation: Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania.
authors.forename: David L
authors.initials: DL
authors.lastname: Diehl
authors.affiliation: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Nirag C
authors.initials: NC
authors.lastname: Jhala
authors.affiliation: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Ginsberg
authors.affiliation: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Maureen
authors.initials: M
authors.lastname: DeMarshall
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Tyler
authors.initials: T
authors.lastname: Foxwell
authors.affiliation: Esophageal and Lung Institute, Allegheny Health Network, Pittsburgh, Pennsylvania.
authors.forename: Blair A
authors.initials: BA
authors.lastname: Jobe
authors.affiliation: Esophageal and Lung Institute, Allegheny Health Network, Pittsburgh, Pennsylvania.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Zaidi
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Duits
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Jacques J G H M
authors.initials: JJ
authors.lastname: Bergman
authors.affiliation: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Anil
authors.initials: A
authors.lastname: Rustgi
authors.affiliation: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Falk
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000473:pathology*; D001471:Barrett Esophagus / Q000453:epidemiology / Q000473:pathology*; D001706:Biopsy; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000473:pathology*; D004945:Esophagoscopy; D004947:Esophagus / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010414:Pennsylvania / Q000453:epidemiology; D011230:Precancerous Conditions; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors