ERYTHROPOIETIN PRODUCTION IN HEPATOCELLULAR-CARCINOMA CELLS ASSOCIATED WITH POLYCYTHEMIA - IMMUNOHISTOCHEMICAL EVIDENCE

Patients with hepatocellular carcinoma sometimes have erythrocytosis a nd high plasma erythropoietin levels. However, previous studies have n ot revealed direct evidence that the carcinoma cells produce the eryth ropoietin. To address this question, we carried out light and electron microscopic immunohistochemical studies, using a human erythropoietin antibody to the liver in three male patients with hepatocellular carc inoma and erythrocytosis. Alpha-Fetoprotein localization was also exam ined in serial liver sections by light microscopic immunohistochemistr y with an antibody to alpha-fetoprotein. All three patients demonstrat ed high hemoglobin levels (16.7, 17.6 and 18.1 gm/dl) and high plasma erythropoietin levels (227, 266 and 280 mU/ml). In one patient the pla sma erythropoietin level in the hepatic vein was significantly higher than that in the hepatic artery. The levels of plasma erythropoietin, as well as such tumor markers for hepatocellular carcinoma as serum al pha-fetoprotein and plasma des-gamma-carboxyprothrombin, were signific antly reduced after treatment with an anticancer drug, cisplatin. Ligh t microscopic immunohistochemistry showed that erythropoietin was defi nitely present in the cytoplasm of the hepatocellular carcinoma cells, but not in normal hepatocytes around the carcinoma lesion or in other nonparenchymal cells such as vascular endothelial cells and Kupffer c ells. In electron microscopic immunohistochemistry, reaction products for erythropoietin were revealed ln the cisternae of the endoplasmic r eticulum in the carcinoma cells, suggesting,the production of erythrop oietin by these cells. Light microscopic immunohistochemistry showed t hat alpha-fetoprotein was localized in the hepatocellular carcinoma ce lls that were erythropoietin positive in the serial sections. These fi ndings indicated that hepatocellular carcinoma cells produced erythrop oietin as well as alpha-fetoprotein in these cases, leading to the com plication of erythrocytosis.