Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis

Ballooned hepatocytes in steatohepatitis: The value of keratin immunohistochemistry for diagnosis

“…Oxidative and nitrosative stress may especially contribute to the pathogenesis of alcoholic and non-alcoholic steatohepatitis, Wilson's disease, primary biliary cirrhosis and hepatocellular carcinoma, conditions in which decrease and loss of the IF cytoskeleton in liver cells have recently been demonstrated [11][12][13]15,31,32]. Moreover, ischemia/reperfusion of the liver allograft triggers the generation of reactive oxygen species through leakage of electrons from the damaged mitochondrial electron transport chain resulting in depletion of reduced glutathione, impairment of superoxide dismutase activity and activation of caspase 3 particularly in centrilobular hepatocytes in the early post transplant period [33,34].…”

“…Antigen retrieval was achieved by microwaving the sections in Target Retrieval Solution, pH 9.0 (Dako REAL TM S2367; Dako, Glostrup, Denmark), for 40 min at 160 W followed by cooling down for 20 min at RT. The sections were washed with tap water and PBS and treated with Dako REAL TM Blocking Solution for 10 min prior to incubation with a mixture of antibodies to K8 and K18 (1:1; mixed monoclonal mouse K8 Ab-8 Clone K8.8, NeoMarkers, Fremont, USA, and monoclonal mouse K18 Ab-1 Clone DC 10, NeoMarkers, both 1:50 in Dako REAL TM Antibody Diluent) or prior to incubation with antibodies to ubiquitin and p62, for 2 hrs at RT, as described previously [13,14,20]. In addition, in order to characterize K, p62 and ubiquitin expression in so-called intermediate hepatocytes, sections of cases with previously diagnosed chronic cholestasis were immunostained using antibodies to K7 (Dako).…”

“…Alterations of the hepatocyte IF cytoskeleton have been reported in alcoholic and non-alcoholic steatohepatitis, Wilson's disease and other types of copper toxicosis, primary biliary cirrhosis, hepatocellular neoplasms and related animal models, e.g. the chronically dicarboxy-diethoxy-dihydrocollidine-fed mouse, in which immunohistochemical analysis using antibodies against K 8 and 18 revealed a disturbance, decrease or even loss of the IF network staining particularly in enlarged (''ballooned") hepatocytes [3,10,[13][14][15].…”

Wilson disease

“…In contrast, stainable amounts of copper may sometimes be even more conspicuous in chronic cholestatic liver diseases, such as primary biliary cirrhosis [28] and primary sclerosing cholangitis [22]; usually, however, they are confined to zone I or to the periphery of parenchymal nodules. The only other non-cholestatic and non-WD liver disorders with high intrahepatic copper levels are Indian childhood cirrhosis and endemic Tyrolean infantile cirrhosis (idiopathic copper toxicosis), both of which are extremely rare conditions, show a specific geographic distribution, and have to be distinguished from WD on both clinical and morphological grounds [43,44,59].…”

The ubiquitin-binding protein p62 is expressed in breast cancers showing features of aggressive disease

“…It has an important function in promoting survival signals, including proliferation, differentiation and induction of anti-apoptotic genes (Ciani et al 2003, Seibenhener et al 2004. Alterations in the nature of p62 have been shown to occur in benign disease states, such as Paget's disease of bone and conditions characterised by intracellular inclusions including Parkinson's, Alzheimer's and Wilson's diseases (Kuusisto et al 2002, 2003, Stumptner et al 2002, Muller et al 2004, Cavey et al 2005. Abnormal expression has been documented in various neoplasms including gastrointestinal, prostate and breast cancers (Stumptner et al 1999, Thompson et al 2003, Qian et al 2005, Kitamura et al 2006.…”