Are the Mallory bodies and intracellular hyaline bodies in neoplastic and non-neoplastic hepatocytes related?
Mallory bodies (MBs) and intracellular hyaline bodies (IHBs) are cytoplasmic hepatocellular inclusions that consist of aggregated proteins. MBs are characteristically associated with alcoholic and non-alcoholic steatohepatitis, but may also be found in chronic cholestatic and metabolic (eg copper intoxication) diseases and hepatocellular neoplasms, particularly hepatocellular carcinomas. IHBs have hitherto only been described in hepatocellular carcinoma cells. In the present study hepatocellular carcinomas (HCCs) and a case of idiopathic copper toxicosis were evaluated with respect to the presence and mutual relationship of MBs and IHBs. IHBs alone were present in 8.6%, MBs alone in 16.1% and both types of inclusion in 7.5% of HCCs. It is shown that IHBs may also occur in non-neoplastic hepatocytes in association with idiopathic copper toxicosis, together with MBs. In HCCs and idiopathic copper toxicosis, MBs and IHBs may be present within the same cell. Moreover, hybrid inclusions holding an intermediate position between MBs and IHBs regarding light microscopy, ultrastructure and composition exist. MBs and IHBs contain p62, a stress-inducible adapter protein, as the major constituent. In MBs p62 is associated with keratins, whereas classical IHBs lack keratins. Light microscopic, electron microscopic and immunohistochemical data suggest a close pathogenetic relationship between MBs and IHBs. Both types of inclusion are the result of over-expression and accumulation of the stress protein p62. If p62 is induced alone, or at least prevails, IHBs may arise by aggregation. However, if abnormal keratins are present in addition to p62, p62 associates and co-aggregates with keratins, finally leading to classical MBs.
Department of Pathology, Medical University of Graz, Graz, Austria. helmut.denk@meduni-graz.at
H
H
Denk
C
C
Stumptner
A
A
Fuchsbichler
T
T
Müller
Gh
G
Farr
W
W
Müller
L
L
Terracciano
K
K
Zatloukal
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000648:ultrastructure*; D056486:Chemical and Drug Induced Liver Injury; D003300:Copper / Q000506:poisoning; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D006818:Hyalin; D002479:Inclusion Bodies / Q000378:metabolism / Q000648:ultrastructure*; D007633:Keratins / Q000378:metabolism; D008107:Liver Diseases / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000648:ultrastructure*; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D009363:Neoplasm Proteins / Q000378:metabolism; D000071456:Sequestosome-1 Protein
D048868:Adaptor Proteins, Signal Transducing; D009363:Neoplasm Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D007633:Keratins; D003300:Copper