Diagnostic impact and reproducibility of p53 immunohistochemistry in Barrett's oesophagus: results of the Dutch Esophageal Pathology Panel ( <scp>DEPP</scp> )

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.