Diagnostic impact and reproducibility of p53 immunohistochemistry in Barrett's oesophagus: results of the Dutch Esophageal Pathology Panel (
DEPP
)
Ylva A. Weeda, Sarah M. Issa, Hans Halfwerk, Michel Botros, Onno J. de Boer, Lodewijk A. Brosens, Michail Doukas, Gursah Kats‐Ugurlu, Fiebo ten Kate, Jaap van der Laan, Ineke van Lijnschoten, Ariadne H. A. G. Ooms, Lindsey Oudijk, Rachel S. van der Post, Mihaela G. Raicu, Bert Timmer, Myrtle J. van der Wel, Sybren L. Meijer Introduction
Evidence supporting the use of p53 immunohistochemistry (p53‐IHC) in Barrett's oesophagus (BE) is largely based on selected series, limiting generalizability. This study evaluates p53‐IHC in a nationwide, real‐world BE‐cohort within a universal healthcare system, assessing concordance with referring hospitals, interobserver agreement (IOA) and its impact on routine diagnostic decisions.
Methods
Revision cases submitted to the Dutch Esophageal Pathology Panel (DEPP) were assessed by trained and experienced pathologists for haematoxylin and eosin (H&E)‐based classification (Vienna classification), p53‐IHC patterns (wild‐type, overexpression, double clone, null mutation and equivocal) and combined H&E/p53‐IHC review. Concordance between referring hospitals and the expert panel (Cohen's kappa) and IOA among panel pathologists (Fleiss' kappa) were assessed, along with the impact of p53‐IHC on diagnostic reclassification.
Results
A total of 1,146 consecutive patient consultation cases (1,704 biopsy levels) were included, with a median of 12 DEPP pathologist assessments per biopsy. Overall concordance of p53 assessment between referring hospitals and the expert panel was moderate‐to‐substantial ( κ = 0.61, 95% CI 0.58–0.64), with 24.2% of p53‐IHC assessments reclassified. IOA among 13 pathologists assessing 316 endoscopic biopsies was substantial ( κ = 0.65, 95% CI 0.61–0.69). Ancillary p53‐IHC influenced pathologists' decisions across biopsy levels. For non‐dysplastic (NDBE) biopsies, aberrant p53‐IHC prompted reclassification to indefinite for dysplasia (IND, 9.2%) or low‐grade dysplasia (LGD, 4.8%). For IND biopsies, p53‐IHC shifted diagnoses toward NDBE (17.0%) or LGD (37.1%).
Conclusion/discussion
p53‐IHC interpretation is reliable, reproducible and clinically meaningful in BE diagnostics when standardized criteria are applied. These findings support broader use of p53‐IHC in routine practice and incorporation of assessment criteria into guidelines.