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

Rebecca J. Critchley-Thorne, Jon M. Davison, Jeffrey W. Prichard, Lia M. Reese, Yi Zhang, Kathleen Repa, Jinhong Li, David L. Diehl, Nirag C. Jhala, Gregory G. Ginsberg, Maureen DeMarshall, Tyler Foxwell, Blair A. Jobe, Ali H. Zaidi, Lucas C. Duits, Jacques J. G. H. M. Bergman, Anil Rustgi, Gary W. Falk

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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
Original languageEnglish
Pages (from-to)240-248
JournalCancer epidemiology, biomarkers & prevention
Issue number2
Early online date2016
Publication statusPublished - 2017

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