Quantitative Evaluation by Digital Pathology of Immunohistochemical Expression of CK7, CK19, and EpCAM in Advanced Stages of NASH

Author:

Cabibi Daniela1ORCID,Giannone Antonino Giulio1ORCID,Quattrocchi Alberto1ORCID,Calvaruso Vincenza2ORCID,Porcasi Rossana1,Di Grusa Domenico1,Pavone Anna Maria3,Comelli Albert3ORCID,Petta Salvatore2

Affiliation:

1. Unit of Anatomic Pathology, Department of Health Promotion Mother and Child Care Internal Medicine and Medical Specialties (PROMISE), University Hospital AOU Policlinico “P. Giaccone”, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy

2. Section of Gastroenterology and Hepatology, Department of Health Promotion Mother and Child Care Internal Medicine and Medical Specialties (PROMISE), University Hospital AOU Policlinico “P. Giaccone”, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy

3. Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy

Abstract

(1) Background: Nonalcoholic Steatohepatitis/Nonalcoholic Fatty Liver Disease (NASH/NAFLD) is the most recurrent chronic liver disease. NASH could present with a cholestatic (C) or hepatic (H) pattern of damage. Recently, we observed that increased Epithelial Cell Adhesion Molecule (EpCAM) expression was the main immunohistochemical feature to distinguish C from H pattern in NASH. (2) Methods: In the present study, we used digital pathology to compare the quantitative results of digital image analysis by QuPath software (Q-results), with the semi-quantitative results of observer assessment (S-results) for cytokeratin 7 and 19, (CK7, CK19) as well as EpCAM expression. Patients were classified into H or C group on the basis of the ratio between alanine transaminase (ALT) and alkaline phosphatase (ALP) values, using the “R-ratio formula”. (3) Results: Q- and S-results showed a significant correlation for all markers (p < 0.05). Q-EpCAM expression was significantly higher in the C group than in the H group (p < 0.05). Importantly ALP, an indicator of hepatobiliary disorder, was the only biochemical parameter significantly correlated with Q-EpCAM. Instead, Q-CK7, but not Q-CK19, correlated only with γGlutamyl-Transferase (γGT). Of note, Stage 4 fibrosis correlated with Q-EpCAM, Q-CK19, and ALP but not with γGT or ALT. Conclusions: Image analysis confirms the relation between cholestatic-like pattern, associated with a worse prognosis, with increased ALP values, EpCAM positive biliary metaplasia, and advanced fibrosis. These preliminary data could be useful for the implementation of AI algorithms for the assessment of cholestatic NASH.

Funder

European Union—NextGenerationEU through the Italian Ministry of University and Research

Publisher

MDPI AG

Reference42 articles.

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