Cell proliferative activity in adenomatous hyperplasia of the liver and small hepatocellular carcinoma. An immunohistochemical study demonstrating proliferating cell nuclear antigen.

BACKGROUND. Recently, adenomatous hyperplasia (AH) of the liver, a sizable parenchymal nodule in the cirrhotic liver, has been considered a preneoplastic lesion in human hepatocarcinogenesis. METHODS. The authors evaluated cell proliferative activity by immunostaining for proliferating cell nuclear antigen (PCNA) in AH (n = 30), small hepatocellular carcinoma (HCC) (n = 14), and their surrounding regenerative nodules (SRN). RESULTS. AH was categorized histologically as ordinary or atypical. Ordinary AH (n = 8) had no hepatocellular atypia, whereas atypical AH (n = 22) was composed of atypical hepatocytes that were equivocal as to benignity and malignancy. Three atypical AH contained overt malignant foci. The PCNA labeling index of ordinary AH was lower than that of SRN and the index of atypical AH was higher than that of SRN except in two cases. The PCNA labeling index of malignant foci within atypical AH was higher than that of nonmalignant areas of atypical AH and was similar to that of small HCC. For small HCC, the PCNA labeling index was much higher than that of SRN and correlated with small HCC grades. CONCLUSIONS. These data suggest that ordinary AH is a largely developed regenerative nodule with little proliferative activity and that it is not a preneoplastic lesion; the data also indicate that atypical AH has much proliferative activity, from which malignant foci with greater proliferative activity emerge. Atypical AH with or without malignant foci may represent an early stage of multi-step hepatocarcinogenesis in humans.