Optimising Expert Pathology Referral in Barrett's Oesophagus Dysplasia Through p53-Guided Triage: A Nationwide Real-World Cohort Study.

Authors

Ylva A Weeda, Myrtle J van der Wel, Lodewijk A Brosens, Ariadne H A G Ooms, Hans Halfwerk, Maartje T P M Houben, Onno J de Boer, Michail Doukas, Fiebo Ten Kate, Gursah Kats-Ugurlu, Jaap van der Laan, Ineke van Lijnschoten, Lindsey Oudijk, Rachel S van der Post, Mihaela G Raicu, Wim Timens, Bert Timmer, Mike Visser, Jacques J G Bergman, Lucas Duits, Sybren L Meijer

Published in

United European gastroenterology journal. Volume 14. Issue 8.

Abstract

Histopathological interpretation of Barrett's oesophagus-associated dysplasia remains variable, and although guidelines recommend expert pathology review, specialist capacity is increasingly constrained. We assessed the real-world diagnostic impact of national expert review and tested whether p53-IHC identifies subgroups in which review is high- or low-yield.
The Dutch Oesophageal Pathology Panel reviewed consecutive BE cases submitted from 39 hospitals (2015-2024). Digitised haematoxylin and eosin-stained and p53-IHC slides were assessed by experienced gastrointestinal pathologists. Panel diagnoses required ≥ 75% agreement or consensus meeting review. Referring and panel diagnoses were compared at the patient level, with biopsy-level analyses assessing diagnostic shifts according to referring-centre p53-IHC status (wild-type, aberrant or equivocal).
The cohort included 1146 consecutive patients and 2187 biopsy levels, each assessed by a median of 12 panel pathologists. Expert review changed 46.9% of referring diagnoses (downgrading 24.7% and upgrading 22.2%). Indefinite for dysplasia (IND) was the most unstable diagnostic category, with 73.4% of cases reclassified. Among 1731 biopsy levels with reported p53-IHC at referral, p53-IHC strongly stratified review yield. Low-grade or high-grade dysplasia (LGD/HGD) with aberrant p53-IHC was confirmed in 91.7% of biopsy levels. In contrast, LGD/HGD with wild-type or equivocal p53-IHC showed substantially higher downgrade rates (53.6% and 32.8%), with odds ratios for diagnostic adjustment of 12.7 (95% CI: 8.2-19.7) and 5.4 (95% CI: 2.9-10.0) versus aberrant p53-IHC.
Expert review substantially altered BE dysplasia diagnoses, supporting current guideline recommendations. P53-IHC markedly stratified review yield: IND and dysplasia with wild-type or equivocal p53-IHC remain high-priority categories, whereas aberrant p53-IHC dysplasia was rarely reclassified. A p53-guided triage strategy could help optimise the use of expert pathology capacity, but prospective validation is needed before clinical implementation.

PMID:
42935139
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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