The dysplasia grading of Barrett's esophagus (BE), based on the histomorphological assessment of formalin-fixed, paraffin-embedded (FFPE) tissue, suffers from high interobserver variability leading to an unsatisfactory prediction of cancer risk. Thus, pre-analytic preservation of biological molecules, which could improve risk prediction in BE enabling molecular and genetic analysis, is needed. We aimed to evaluate such a molecular pre-analytic fixation tool, PAXgene-fixed paraffin-embedded (PFPE) biopsies, and their suitability for histomorphological BE diagnostics in comparison to FFPE. In a ring trial, 9 GI pathologists evaluated 116 digital BE slides of non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and esophageal adenocarcinomas (EAC) using virtual microscopy. Overall quality, cytological and histomorphological parameters, dysplasia criteria, and diagnosis were analyzed. PFPE showed better preservation of nuclear details as chromatin and nucleoli, whereas overall quality and histomorphologic parameters as visibility of basal lamina, goblet cells, and presence of artifacts were scored as equal to FFPE. The interobserver reproducibility with regard to the diagnosis was best for NDBE and EAC (κF = 0.72-0.75) and poor for LGD and HGD (κF = 0.13-0.3) in both. In conclusion, our data suggest that PFPE allows equally confident histomorphological diagnosis of BE and EAC, introducing a novel tool for molecular analysis and parallel histomorphological evaluation.

Department of Medicine 2 Universitaetsklinikum Freiburg Freiburg Germany

Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston USA

Department of Pathology Michigan Medicine Ann Arbor MI USA

Department of Pathology PathWest Laboratory University of Western Australia WA Perth Australia

Department of Pathology Yaroslavl Regional Cancer Hospital Yaroslavl Russian Federation

Institute for Pathology Friedrich Alexander University Erlangen Nuremberg Klinikum Bayreuth Bayreuth Germany

Institute for Surgical Pathology Medical Center University of Freiburg and Faculty of Medicine University of Freiburg 79106 Freiburg Germany

Institute of Pathology and Molecular Diagnostics University Medical Center Augsburg Augsburg Germany

Institute of Pathology Technical University of Munich Munich Germany

Klinikum Rechts Der Isar Medical Clinic and Polyclinic 2 Technical University of Munich Munich Germany

Service d'Anatomie Pathologique AP HP Faculté de Médecine Sorbonne Hôpital Saint Antoine Université 75012 Paris France

The Fingerland Department of Pathology Faculty of Medicine and University Hospital Charles University Hradec Králové Czech Republic

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