Optimising Expert Pathology Referral in Barrett's Oesophagus Dysplasia Through p53‐Guided Triage: A Nationwide Real‐World Cohort Study
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. MeijerABSTRACT
Background
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.
Methods
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).
Results
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.
Conclusion
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.