Copper and hepatocellular carcinoma.

The presence of copper and copper-binding protein (CBP) within tumor cells was searched by histochemical methods (rhodanine, rubeanic acid and Shikata's orcein) in a group of 39 autopsies, all consecutive cases of hepatocellular carcinoma (HCC) associated with cirrhosis (HCC + C). In 2 cases, fibrolamellar carcinoma (FLC) not associated with cirrhosis was observed at surgery. Considerable amounts of copper and CBP were found within tumor cells only in the 2 FLC cases and in 1 HCC + C case, in a portion of the tumor showing FLC-like features. Copper-positive tumor cells had an oncocytic appearance, which was confirmed by ultrastructural examination. In 64% of the HCC + C cases (25 out of 39), copper and CBP deposits were found in nonneoplastic hepatocytes mainly distributed along the periphery of cirrhotic nodules. The present study indicates that the storage of copper inside tumor cells is a peculiarity of the FLC type of HCC with a close relationship to the oncocytic nature of neoplastic hepatocytes. The significance of copper deposits in nonneoplastic cirrhotic hepatocytes remains a matter for further investigations.