Histochemical and ultrastructural study of copper-binding protein in hepatocellular carcinoma

Orcein-positive hepatocellular material (OPHM), found in 18 of 44 hepatocellular carcinomas (HCC), was compared histochemically and ultrastructurally with similar granular materials in other liver diseases. OPHM was not found in 15 control livers, 45 metastatic liver cancers or ten cholangiocellular carcinomas. OPHM in HCC was stained with orcein when the tissue sections were preoxidized. In addition, it was positively stained with rhodanine and rubeanic acid for copper. These findings were identical to the OPHM in Wilson's disease, in primary biliary cirrhosis and in neonatal livers. Seven of 12 resected HCC revealed cytoplasmic dense bodies ultrastructurally in which an x-ray microanalyzer demonstrated copper. OPHM in HCC, a granular accumulation, was concluded to be rich in copper-protein complex, and might correspond to dense bodies derived from lysosome ultrastructurally. The pathogenesis and biologic significance of this copper overload in a number of HCC are also discussed.