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Hepatocellular carcinomas with intracellular hyaline bodies have a poor prognosis

2016-11-25 14:31:01

Liver International; 25 November 2016: DOI:10.1111/liv.13325

Ariane Aigelsreiter, Jens Neumann, Martin Pichler, Judith Halasz, Kurt Zatloukal, Andrea Berghold, Philipp Douschan, Florian Rainer, Rudolf Stauber, Johannes Haybaeck, Helmut Denk, Carolin Lackner



Abstract


Background and Aims


Mallory-Denk-bodies (MDB) and intracellular hyaline bodies (IHB) are cytoplasmic inclusions found in a subset of hepatocellular carcinoma (HCC). MDB are mainly composed of the intermediate filament proteins keratin (K) 8 and K18, the cellular stress- and adapter-protein sequestosome 1/p62 (p62) and ubiquitin, whereas IHB consist of p62 and/or ubiquitin. Of note, cytoplasmic inclusions containing p62 can serve as markers of suppressed autophagy which in turn has been associated with poor prognosis. The aim of this study was to evaluate the prognostic significance of p62-containing MDB and IHB in patients with HCC.



Methods


Ninety resected HCCs were assessed by H&E histology for MDB or IHB and their presence was confirmed by immunohistochemistry using K8/18, p62 and ubiquitin antibodies. The prognostic impact of inclusions was assessed using Kaplan-Meier and multivariate Cox proportional model.



Results


MDB and/or IHB were found in about 50% of HCC. Both types of inclusions were seen in 21%, MDB only in 19% and IHB only in 10% of cases. The presence of MDB in tumours was associated with the steatohepatitic variant of HCC, which also showed fatty change, ballooning of tumour cells, MDBs, inflammation and pericellular fibrosis (p <0.001). In contrast, IHB were not associated with steatohepatitic morphology but were associated with significantly shorter overall survival (p=0.006). Multivariate analysis revealed macroscopic vascular invasion (p=0.045) and presence of IHB in HCC cells (p=0.005) as independently associated with overall survival.



Conclusions


IHB and macroscopic vascular invasion identify a subset of HCC patients with poor prognosis. This article is protected by copyright. All rights reserved.



Empire Genomics IDetect SUPER STAIN HRP POLYMER KIT was used in this publication.

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