Immunohistochemical characterization of hepatoblasomas in B6C3F1 mice treated with diethylnitrosamine and sodium phenobarbital

Hepatoblastomas (HBs) were induced in B6C3F1 mate mice by diethylnitrosamin e (DEN) and sodium phenobarbital (PB). Six-week-old mice received a single intraperitoneal dose of DEN followed by a continuous treatment with PB in d iet at a concentration of 0 (group 1) or 500 (group 2) ppm for 50 weeks. HB s were observed in 13 of 21 (62%) group 2 mice, with typical histologic fea tures as reported previously, while no such tumors were observed in group 1 . Seven of 13 (54%) HBs were found in and/or adjacent to hepatocellular ade nomas (HCAs) or hepatocellular carcinomas (HCCs). Immunohistochemically, al l HBs were positive for S-100 protein but negative for keratin, alpha -feto protein (AFP). albumin (ALB) and vimentin, while HCC cells occasionally rea cted positively for AFP with a mosaic pattern. HCC and HCA cells were occas ionally positive for ALB. Non-neoplastic hepatocytes and normal bile ducts were positively stained for ALB and keratin/S-100 protein, respectively. S- 100 protein is known to be expressed in many mesenchymal tissues and neopla sms including neuroectodermal elements but negative in cells of the hepatic lineage. Thus. the present immunohistochemical results suggested that mese nchymal differentiation occurs in mouse HB cells as observed in human HBs, one of the most frequent infant liver tumors in humans. Although the suscep tibility of mouse HBs to PB-promotion suggests a hepatocytic histogenesis, the present immunohistochemical results support the hypothesis that the mou se HB is derived from pluripotent endodermal stem-like cells.