The utility of P53 immunohistochemistry in the diagnosis of Barrett's esophagus with indefinite for dysplasia.

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Januszewicz, Wladyslaw  ORCID logo
Pilonis, Nastazja D 
Sawas, Tarek 
O'Donovan, Maria 

BACKGROUND: Barrett's esophagus with indefinite for dysplasia (BE-IND) is a subjective diagnosis with a low interobserver agreement (IOA) among pathologists and uncertain clinical implications. This study aimed to assess the utility of p53 immunohistochemistry (p53-IHC) in assessing BE-IND specimens. METHODS: Archive endoscopic biopsies with a BE-IND diagnosis from two academic centers were analyzed. Firstly, hematoxylin and eosin-stained slides (H&E) were reviewed by four expert GI pathologists allocated into two groups (A and B). After a wash-out period of at least eight weeks, H&E slides were re-assessed side-to-side with p53-IHC available. We compared the rate of changed diagnosis and the IOA for all BE grades before and after p53-IHC. FINDINGS: We included 216 BE-IND specimens from 185 patients, of which 44.0% and 32.9% were confirmed after H&E slide revision by Groups A and B, respectively. Over half of the cases were reclassified to a non-dysplastic BE (NDBE), while 5.6% of cases in Group A and 7.4% in Group B were reclassified to definite dysplasia. The IOA for NDBE, BE-IND, low-grade dysplasia (LGD), and high-grade dysplasia (HGD)/intramucosal cancer (IMC) was 0.31, 0.21, -0.03, and -0.02, respectively. Use of p53-IHC led to a >40% reduction in BE-IND diagnoses (P<.001), and increased IOA for all BE grades (κ=0.46 [NDBE], 0.26 [BE-IND], 0.49 [LGD], 0.35 [HGD/IMC]). An aberrant p53-IHC pattern significantly increased the likelihood of reclassifying BE-IND to definite dysplasia (odds ratio 44.3, 95%CI:18.8-113.0). INTERPRETATION: P53-IHC reduces the rate of BE-IND diagnoses and improves the IOA among pathologists when reporting BE with equivocal epithelial changes.

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This study received infrastructure support from the NIHR Cambridge Biomedical Research Centre