De novo expression of nonhepatocellular cytokeratins in Mallory body formation.

Abstract

Mallory bodies (MBs) are eosinophilic cytoplasmic inclusions observed predominantly in alcoholic liver disease. Although linked to disease activity, their pathogenesis is still unclear. Since intermediate filaments (cytokeratins) are major components of MBs, their cytokeratin polypeptide composition was analysed with monospecific antibodies for cytokeratins 7, 8, 14, 18, 19, and 20 by immunohistology. MBs were identified by light microscopy and ubiquitin immunostaining. All MBs were positive for cytokeratins 8 and 18. A significant percentage of the MBs was strongly positive for cytokeratins 19 and/or 20, which are not detectable in hepatocytes of normal liver and, in the case of cytokeratin 20, in hepatocytes of diseases devoid of MBs. MBs were essentially negative for cytokeratins 7 and 14. De novo expression of cytokeratins 19 and 20 was independent of the aetiology, occurring in all MB-associated diseases analysed, and seemed to precede MB formation, since in some hepatocytes a cytoskeletal-type staining pattern for these cytokeratins was present. In hepatocellular carcinomas cytokeratins 19 and 20 were frequently detected, but their cellular distribution was less closely associated with MBs. The ectopic expression of cytokeratins 19 and 20 appears to be related to MB formation and may take part in the derangement of the intermediate filaments during MB formation.