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Schwertheim et al. Hepatoma Res 2020;6:41 Hepatoma Research
DOI: 10.20517/2394-5079.2020.23

Original Article Open Access

β-catenin in intranuclear inclusions of hepatocellular
carcinoma

Suzan Schwertheim , Holger Jastrow , Julia Kälsch , Thomas Herold , Sarah Theurer , Saskia Ting , Kurt
1
1
1
1,3
1
2
Werner Schmid , Hideo Andreas Baba 1
1,4
1 Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany.
2 Institute of Anatomy and Electron Microscopy Unit of Imaging Center Essen, University Hospital of Essen, University of
Duisburg-Essen, Essen 45147, Germany.
3 Department of Gastroenterology and Hepatology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147,
Germany.
4 Member of the West German Cancer Centre Essen (WTZE), University Hospital of Essen, University of Duisburg-Essen, Essen
45147, Germany.
Correspondence to: Dr. Hideo Andreas Baba, Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen,
Hufelandstr 55, Essen 45147, Germany. E-mail: hideo.baba@uk-essen.de
How to cite this article: Schwertheim S, Jastrow H, Kälsch J, Herold T, Theurer S, Ting S, Schmid KW, Baba HA. β-catenin in
intranuclear inclusions of hepatocellular carcinoma. Hepatoma Res 2020;6:41. http://dx.doi.org/10.20517/2394-5079.2020.23
Received: 9 Mar 2020 First Decision: 22 Apr 2020 Revised: 5 May 2020 Accepted: 20 May 2020 Published: 10 Jul 2020

Academic Editor: Guido Guenther Gerken Copy Editor: Cai-Hong Wang Production Editor: Tian Zhang

Abstract
Aim: β-catenin activation is known to promote liver regeneration and play a role in the pathogenesis of liver cancer.
Recently, we detected intranuclear inclusions (NI) in hepatocellular carcinoma (HCC) containing degenerated
cell organelles and lysosomal proteins and delimited by a completely closed nuclear membrane. The presence
of NI was positively associated with patient survival. The aim of the current study was to investigate a possible
association between proteins of the Wnt/β-catenin pathway with NI morphology and survival.

Methods: We examined NI in 72 paraffin-embedded specimens of HCC. Immunohistochemistry (IHC) and
immunofluorescence (IF) were performed to investigate the content and shape of NI. β-catenin gene (CTNNB1 )
mutations were analyzed by next generation sequencing.

Results: We detected the accumulation of β-catenin and glutamine synthetase (a target gene of β-catenin)
proteins within NI. Further, we found immunopositivity for the lysine demethylase KDM2A in NI. KDM2A is known
to be involved in β-catenin degradation. We detected significant associations between the presence of β-catenin
and autophagy-associated proteins in NI. Double-IF revealed co-localization of β-catenin and p62 in the same
NI. Kaplan-Meier survival analysis showed that the presence of NI containing KDM2A protein accumulations
displayed a significant benefit in overall survival.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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