Independent Blinded Validation of a Tissue Systems Pathology Test to Predict Progression in Patients With Barrett's Esophagus

Am J Gastroenterol. 2020 Jun;115(6):843-852. doi: 10.14309/ajg.0000000000000556.

Abstract

Introduction: A risk prediction test was previously validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). The aim of our study was to independently validate this test to predict the risk of progression to HGD/EAC in BE patients with nondysplastic (ND), indefinite for dysplasia and low-grade dysplasia (LGD).

Methods: A single-blinded, case-control study was conducted to stratify patients with BE as low, intermediate, or high risk for progression to HGD/EAC within 5 years using a previously described risk prediction test. Patients with BE who progressed to HGD/EAC after at least 1 year (n = 58) were matched to patients undergoing surveillance without progression (n = 210, median surveillance 7 years). Baseline biopsies with subspecialist diagnoses of ND, indefinite for dysplasia, or LGD were tested in a blinded manner, and the predictive performance of the test was assessed.

Results: This risk prediction test stratified patients with BE based on progression risk with the high-risk group at 4.7-fold increased risk for HGD/EAC compared with the low-risk group (95% confidence interval 2.5-8.8, P < 0.0001). Prevalence-adjusted positive predictive value at 5 years was 23%. The high-risk class and male sex provided predictive power that was independent of pathologic diagnosis, age, segment length, and hiatal hernia. Patients with ND BE who scored high risk progressed at a higher rate (26%) than patients with subspecialist-confirmed LGD (21.8%) at 5 years.

Discussion: A risk prediction test identifies patients with ND BE who are at high risk for progression to HGD/EAC and may benefit from early endoscopic therapy or increased surveillance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adenocarcinoma / epidemiology*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Barrett Esophagus / metabolism
  • Barrett Esophagus / pathology*
  • Biomarkers / metabolism
  • CD68 Molecule
  • Case-Control Studies
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Disease Progression
  • Erb-b2 Receptor Tyrosine Kinases / metabolism
  • Esophageal Neoplasms / epidemiology*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophagus / metabolism
  • Esophagus / pathology*
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Image Processing, Computer-Assisted
  • Keratin-20 / metabolism
  • Leukocyte Common Antigens / metabolism
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Racemases and Epimerases / metabolism
  • Risk Assessment
  • Tumor Suppressor Protein p53 / metabolism
  • Watchful Waiting

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclooxygenase 2
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Keratin-20
  • Leukocyte Common Antigens
  • Racemases and Epimerases
  • Erb-b2 Receptor Tyrosine Kinases
  • Tumor Suppressor Protein p53
  • CD68 antigen, human
  • CD68 Molecule
  • CDKN2A protein, human
  • HIF1A protein, human
  • TP53 protein, human
  • ERBB2 protein, human
  • alpha-methylacyl-CoA racemase

Supplementary concepts

  • Adenocarcinoma Of Esophagus