1. A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.
- Author
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Critchley-Thorne RJ, Duits LC, Prichard JW, Davison JM, Jobe BA, Campbell BB, Zhang Y, Repa KA, Reese LM, Li J, Diehl DL, Jhala NC, Ginsberg G, DeMarshall M, Foxwell T, Zaidi AH, Lansing Taylor D, Rustgi AK, Bergman JJ, and Falk GW
- Subjects
- Adenocarcinoma diagnosis, Adenocarcinoma metabolism, Adult, Aged, Barrett Esophagus metabolism, Barrett Esophagus pathology, Biopsy, Case-Control Studies, Esophageal Neoplasms diagnosis, Esophageal Neoplasms metabolism, Esophagus metabolism, False Positive Reactions, Female, Humans, Male, Microscopy, Fluorescence, Middle Aged, Prognosis, Barrett Esophagus diagnosis, Biomarkers, Tumor analysis, Disease Progression, Esophagus pathology, Fluorescent Antibody Technique methods
- Abstract
Background: 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., Methods: 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., Results: 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., Conclusion: We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables., Impact: 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., (©2016 American Association for Cancer Research.)
- Published
- 2016
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