Immunocytochemical investigation of alpha-fetoprotein-positive cells in hepatocarcinogenesis and hepatomas induced by 3'-ME-DAB.

AFP-positive cells during 3'-Me-DAB hepatocarcinogenesis and in hepatomas induced by 3'-Me-DAB were observed by the light microscope immunoperoxidase method, and the location of AFP-immunoreaction products in hepatocytes was determined by the electron microscope immunoperoxidase method. Simultaneously serum concentrations of AFP were measured by radioimmunoassay. Serum concentrations of AFP during hepatocarcinogenesis showed a biphasic pattern, and proliferation of cholangiolar cells in the periportal areas was associated with the first peak of serum AFP in the early stage of hepatocarcinogenesis. AFP-containing cells in the late stage were distributed in clusters in the peripheral areas of hyperplastic nodules. The clusters were composed of two different types of AFP-positive cells, one atypical in shape and structure and the other preserving the structure of hepatic cords. In neoplasms, a heterogeneous AFP immunoreaction was recognized in hepatoma cells. In non-neoplastic nodules, cholangiofibrosis surrounded by AFP-positive cholangiolar cells developed. Ultrastructural immunoperoxidase studies revealed immunoreaction products of AFP on the membrane of r-ER, outer nuclear membrane, s-ER and Golgi complex in hepatocytes of hyperplastic nodules as well as of hepatocellular carcinoma cells. It is suggested that cholangiolar cells detected in hepatocarcinogenesis may form proliferating bile ductules, and the appearance of a cluster in association with AFP in hyperplastic nodules supports the hypothesis that some hyperplastic nodules with clusters of AFP-positive cells are important cell populations which may develop into hepatocellular carcinoma.