title: Hepatocellular carcinomas with intracellular hyaline bodies have a poor prognosis.
abstract: Mallory-Denk bodies (MDBs) and intracellular hyaline bodies (IHBs) are cytoplasmic inclusions found in a subset of hepatocellular carcinoma (HCC). MDBs 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 IHBs 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.
  
  
  
  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.
  
  
  
  Mallory-Denk bodies 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<.001). In contrast, IHBs were not associated with steatohepatitic morphology but were associated with significantly shorter overall survival (P=.006). Multivariate analysis revealed macroscopic vascular invasion (P=.045) and presence of IHB in HCC cells (P=.005) as independently associated with overall survival.
  
  
  
  Intracellular hyaline bodies and macroscopic vascular invasion identify a subset of HCC patients with poor prognosis.
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Ariane
authors.initials: A
authors.lastname: Aigelsreiter
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.|Institute of Pathology, Ludwig-Maximilian University of Munich, Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.affiliation: Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.affiliation: 2nd Department of Pathology, Semmelweis University of Budapest, Budapest, Hungary.
authors.forename: Judith
authors.initials: J
authors.lastname: Halasz
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Zatloukal
authors.affiliation: Institute for Medical Informatics Statistics and Documentation, Medical University of Graz, Graz, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Berghold
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Douschan
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Rainer
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stauber
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Denk
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Lackner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000368:Aged; D001317:Austria; D001343:Autophagy; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism*; D053538:Keratin-18 / Q000378:metabolism; D053533:Keratin-8 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D000071456:Sequestosome-1 Protein / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053538:Keratin-18; D053533:Keratin-8; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein
keywords: Mallory-Denk body; autophagy; hepatocellular carcinoma; intracellular hyaline body; prognosis