Light and Electron Microscopic Immunohistochemistry of Transferrin Receptor and Its Serum Level in Human Hepatocellular Carcinoma

The localization of transferrin receptor (TFR) in human hepatocellular carcinoma (HCC) was investigated by light and electron microscopic immunohistochemistry and its serum level was measured by an enzyme-linked immunosorbent assay. TFR expression was observed light microscopically on the plasma membrane and in the cytoplasm. Its staining pattern varied from the membranous type to the cytoplasmic type with degradation of differentiation in HCC. Electron microscopically, TFR was found in the small vesicles located below the plasma membrane, in the dilated endoplasmic reticulum, and in the Golgi complex. The vesicles containing TFR were observed below the plasma membrane in well differentiated HCC, but were found diffusely in the cytoplasm in poorly differentiated HCC. These findings correlated well with the light microscopical TFR stainings. These localizations of TFR were compatible with TFR recycling for iron uptake and TFR synthesis. They also clarified that the less differentiated an HCC was, the more activated were TFR recycling and its synthesis for increased iron demand. Therefore, this study demonstrates a correlation between TFR expression and the grade of differentiation in HCC. The serum levels of soluble TFR in HCC cases were higher than normal, but they showed no correlation with the grade of differentiation