Studies on the proliferative activity of diethylnitrosamine-induced hepatocellular carcinomas in monkeys

In this study, synthetic phase fractions (SPFs) determined by flow cytometry and AgNOR counts were analysed in benign liver lesions (regenerative nodules and adenomas), hepatocellular carcinomas (HCCs), and lung metastases of a monkey hepatocarcinogenesis model to find out if AgNOR counts and SPFs can discriminate between malignant and non-malignant liver lesions. The average per cent SPF values and the AgNOR counts were significantly (P = 0.001) increased in regenerative liver nodules (5.30 per cent; 4.96), adenomas (5.34 per cent; 3.46) and well-differentiated HCCs (6.75 per cent; 4.47), compared with the untreated control livers (3.18 per cent; 0.98), but the differences between these three groups were not significant. In the poorly differentiated HCC group, however, the average SPF value (9.60 per cent) and AgNOR count (7.14) were significantly higher than in any of the other liver lesions examined. A significant correlation was found between the SPF values and AgNOR counts on the one hand, and differentiation and cytological grade of the HCC samples on the other. The results of this study show that the SPF values and AgNOR counts are not reliable in differentiating between regenerating liver nodules, adenomas, and experimental well-differentiated HCCs. The SPF value, however, may serve as a prognostic factor in HCC, since it was found to be significantly higher in HCCs with lung metastasis than in those without.