A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus

Cancer Epidemiol Biomarkers Prev. 2017 Feb;26(2):240-248. doi: 10.1158/1055-9965.EPI-16-0640. Epub 2016 Oct 11.

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Impact: 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.

Publication types

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

MeSH terms

  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / pathology*
  • Barrett Esophagus / epidemiology
  • Barrett Esophagus / pathology*
  • Biopsy
  • Case-Control Studies
  • Cell Transformation, Neoplastic / pathology*
  • Disease Progression
  • Esophageal Neoplasms / epidemiology
  • Esophageal Neoplasms / pathology*
  • Esophagoscopy
  • Esophagus / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Netherlands / epidemiology
  • Pennsylvania / epidemiology
  • Precancerous Conditions*
  • Prevalence
  • Prognosis
  • Risk Assessment*
  • Risk Factors
  • Time Factors

Supplementary concepts

  • Adenocarcinoma Of Esophagus