p53 immunohistochemistry in Barrett's was reproducible across a national panel and changed diagnoses

Design

Nationwide retrospective review of expert panel consultations

Population

1,146 Barrett's oesophagus consultation cases (1,704 biopsy levels) in the Netherlands

Primary outcome

Concordance and interobserver agreement of p53 patterns; diagnostic reclassification

Effect

Interobserver kappa 0.65 (95% CI 0.61 to 0.69); indefinite biopsies reclassified to LGD 37.1%, to non-dysplastic 17.0%

The Dutch Esophageal Pathology Panel reviewed 1,146 consecutive Barrett's oesophagus consultation cases (1,704 biopsy levels), each assessed by a median of 12 expert pathologists on H&E, on p53 immunohistochemistry patterns and on the two together. It appeared in Histopathology on 19 June 2026.

Agreement on p53 pattern between referring hospitals and the panel was moderate to substantial (kappa 0.61), and about a quarter of referring p53 readings were reclassified. Among 13 panel pathologists scoring 316 biopsies, agreement was substantial (kappa 0.65). p53 changed decisions. In biopsies called non-dysplastic on H&E, an aberrant pattern moved 9.2% to indefinite and 4.8% to low-grade dysplasia. In biopsies called indefinite, p53 moved 37.1% to low-grade dysplasia and 17.0% to non-dysplastic.

The indefinite category is where Barrett's surveillance stalls, and this shows p53 resolves a large share of it. The study measured agreement and reclassification, not progression, so it does not prove the reclassified patients fared differently. It does show that, read against agreed criteria, p53 is reliable enough to use routinely as an adjunct.

• Consider p53 immunohistochemistry on Barrett's biopsies that are indefinite for dysplasia or suspicious for low-grade dysplasia.
• Report the p53 pattern by name: wild-type, overexpression, null, double clone or equivocal.
• Recognise the null pattern: complete absence of staining with a positive internal control is aberrant, not negative.
• Seek expert review for any low-grade dysplasia diagnosis, as most guidelines advise.

Why it matters

It turns indefinite-for-dysplasia from a holding category into a decision for more than half of such biopsies.

Don't overread it

The study measured agreement and reclassification, not whether reclassified patients were more likely to progress.

The statistics, in plain English

Kappa measures agreement beyond chance: 0 is chance, 1 is perfect. Values of 0.61 to 0.80 are conventionally called substantial. This is good for a morphological call but still means pathologists disagree on a meaningful minority of cases.

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