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

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

来源：Cancer Epidemiology Biomarkers & Prevention, 2017, 26(2): 240-248.

DOI：10.1158/1055-9965.EPI-16-0640

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.

• 出版日期2017-2