title: A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.
abstract: Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia.
  
  
  
  We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set.
  
  
  
  A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression.
  
  
  
  We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables.
  
  
  
  The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©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 Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Duits
authors.affiliation: Department of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Prichard
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Davison
authors.affiliation: Esophageal and Lung Institute, Allegheny Health Network, Pittsburgh, Pennsylvania.
authors.forename: Blair A
authors.initials: BA
authors.lastname: Jobe
authors.affiliation: Cernostics, Inc., Pittsburgh, Pennsylvania.
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Campbell
authors.affiliation: Cernostics, Inc., Pittsburgh, Pennsylvania.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cernostics, Inc., Pittsburgh, Pennsylvania.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Repa
authors.affiliation: Cernostics, Inc., Pittsburgh, Pennsylvania.
authors.forename: Lia M
authors.initials: LM
authors.lastname: Reese
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
authors.initials: G
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: Ali H
authors.initials: AH
authors.lastname: Zaidi
authors.affiliation: Drug Discovery Institute and Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: D
authors.initials: D
authors.lastname: Lansing Taylor
authors.affiliation: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
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: Gary W
authors.initials: GW
authors.lastname: Falk
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D016022:Case-Control Studies; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D005189:False Positive Reactions; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor