Cytokeratin 8/18 is a useful immunohistochemical marker for hepatocellular proliferative lesions in mice

In order to clarify whether cytokeratin (CK) 8/18 is a useful immunohistochemical marker for hepatocellular proliferative lesions in mice, partially hepatectomized male ICR mice were given 0.6% piperonyl butoxide (PBO) for 8 (Experiment I) or 25 weeks (Experiment II) after N-diethylnitrosamine (DEN) initiation treatment, and the livers were subjected to histological examinations on hematoxylin and eosin (HE) stained sections, CK8/18 immunohistochemistry and gamma-glutamyl transpeptidase (GGT) histochemistry. In Experiment I, the multiplicity of hepatocellular foci in paraffin-embedded sections which were observed in HE-stained sections and positive for CK8/18 was 10.17 and 18.50, respectively, while that of hepatocellular foci in frozen sections which were observed in HE-stained sections and positive/negative for GGT was 6.17 and 8.17, respectively. In Experiment II, the total multiplicity of hepatocellular foci in paraffin-embedded sections which were observed in HE-stained sections and positive/negative for CK8/18 was 4.47 and 23.17, respectively, while that of hepatocellular foci in frozen sections which were observed in HE-stained sections and positive/negative for GGT was 2.50 and 3.50, respectively. Most of the hepatocellular adenomas and carcinomas observed in HE-stained sections were positive for CK8/18, but some of the adenomas were negative for CK8/18. These findings indicate that more hepatocellular proliferative lesions can be detected in CK8/18 immunohistochemistry in addition to those observed in HE-stained sections, and suggest that CK8/18 may become a useful immunohistochemical marker for detecting hepatocellular proliferative lesions in mice.