A retrospective evaluation of spontaneous hepatocellular tumors in B6C3F, mice of 9 two-year and 4 seventy eight-week carcinogenicity studies was conducted. The incidences of hepatocellular adenomas and carcinomas (HCCs) in males were significantly higher than those in females in both series, and development of less-well-differentiated carcinomas with metastases was clearly linked to aging.
PCNA positive indices of well-differentiated HCCs were significantly higher than those of hepatocyte foci, hepatocellular adenomas, and moderately differentiated HCCs. This parameter was useful for the definition of foci and adenomas because in these cases the PCNA positive cells demonstrated a uniform distribution pattern. The number of AgNOR dots tended to increase in accordance with the progression of hepatocarcinogenesis, with bizarre-irregularly shaped forms found in the nuclei of moderately differentiated HCC cells. This parameter therefore appears to be useful for evaluation of the degree of malignancy in hepatocellular carcinomas.
While no c-H-ras protein expression could be detected in 9 cases of well-differentiated HCCs examined in the present study, 18 to 50% of preneoplastic lesions (foci) and neoplastic lesions including adenoma, carcinoma within adenoma, and moderately differentiated HCC.
The present study showed that assessment of the atypical grade in HCC is paramount for evaluation of malignancy, requiring appropriate methods for objective diagnosis.