Prediction of Progression in Barrett's Esophagus Using a Tissue Systems Pathology Test: A Pooled Analysis of International Multicenter Studies

Prasad G. Iyer, D. Chamil Codipilly, Apoorva K. Chandar, Siddharth Agarwal, Kenneth K. Wang, Cadman L. Leggett, Laureano Rangel Latuche, Phillip J. Schulte

Research output: Contribution to journalArticlepeer-review


Background & Aims: Prediction of progression risk in Barrett's esophagus (BE) may enable personalized management. We aimed to assess the adjunct value of a tissue systems pathology test (TissueCypher) performed on paraffin-embedded biopsy tissue, when added to expert pathology review in predicting incident progression, pooling individual patient-level data from multiple international studies Methods: Demographics, clinical features, the TissueCypher risk class/score, and progression status were analyzed. Conditional logistical regression analysis was used to develop multivariable models predicting incident progression with and without the TissueCypher risk class (low, intermediate, high). Concordance (c-) statistics were calculated and compared with likelihood ratio tests to assess predictive ability of models. A risk prediction calculator integrating clinical variables and TissueCypher risk class was also developed. Results: Data from 552 patients with baseline no (n = 472), indefinite (n = 32), or low-grade dysplasia (n = 48) (comprising 152 incident progressors and 400 non-progressors) were analyzed. A high-risk test class independently predicted increased risk of progression to high-grade dysplasia/adenocarcinoma (odds ratio, 6.0; 95% confidence interval, 2.9–12.0), along with expert confirmed low-grade dysplasia (odds ratio, 2.9; 95% confidence interval, 1.2–7.2). Model prediction of progression with the TissueCypher risk class incorporated was significantly superior than without, in the whole cohort (c-statistic 0.75 vs 0.68; P < .0001) and the nondysplastic BE subset (c-statistic 0.72 vs 0.63; P < .0001). Sensitivity and specificity of the high risk TissueCypher class were 38% and 94%, respectively. Conclusions: An objective tissue systems pathology test high-risk class is a strong independent predictor of incident progression in patients with BE, substantially improving progression risk prediction over clinical variables alone. Although test specificity was high, sensitivity was modest.

Original languageEnglish (US)
Pages (from-to)2772-2779.e8
JournalClinical Gastroenterology and Hepatology
Issue number12
StatePublished - Dec 2022


  • Biomarker
  • Esophageal Cancer
  • Screening
  • Surveillance

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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