ANALYSIS OF HYPERPLASTIC FOCI IN LIVERS WITH HEPATOCELLULAR CARCINOMAS BY FLOW-CYTOMETRY AND AGNOR STAINING

The phase S ratio in cell cycles were analyzed in livers with hyperpla stic foci (HPF) and in livers without HPF by nuclear DNA determination s using flow cytometry, and by staining with argyrophilic proteins of the nucleolar organizer region (AgNOR). Flow cytometric analysis was d one on 50 fresh frozen specimens of livers resected from 50 patients w ith hepatocellular carcinoma (HCC). Paraffin sections from the same pa tients were analyzed using AgNOR staining. There were 25 cases each wi th and without HPF. We examined the stage of fibrosis and the grade of inflammatory activity according to the modified Scheuer and Desmet sc ale. The incidence of HCC recurrence among these patients was also stu died. The average phase S ratio of the livers of the patients with HPF was 6.5+/-3.2%, and that of the livers of the patients without HPF wa s 4.0+/-2.5%. The ratio differed significantly between the two groups (P<0.01). The average AgNOR score for HPF lesions of the HPF-positive cases was 1.60+/-0.34, that for non-HPF lesions in the HPF-positive ca ses was 1.29+/-0.12, and that for the HPF-negative cases was 1.19+/-0. 14. Significant differences were found between the average AgNOR score s for HPF lesions of the HPF-positive cases and the non-HPF lesions of the HPF-positive cases (P<0.01), as well as between the non-HPF lesio ns in the HPF-positive cases and the HPF-negative cases (P<0.05). Seve re fibrosis (stage 3) and cirrhosis (stage 4) were found in 76% of HPF -positive cases and 48% of HPF-negative cases. The livers of HPF-posit ive patients were significantly more cirrhotic than those of HPF-negat ive patients (P<0.05). The association between HPF and the inflammator y grade was not significant (P>0.05). The incidence of HCC recurrence among HPF-positive cases was significantly higher than that among the HPF-negative cases (P<0.05). The average phase S ratio of the recurren t HPF-positive patients was 7.48+/-3.48%, significantly higher than th at of HPF negative cases (5.57+/-3.06%, P<0.05). Hyperplastic foci of the liver was shown to be a highly proliferative lesion. The prolifera tive activity of the non-HPF lesions in the HPF-positive patients was also higher than that of the HPF-negative patients. Hyperplastic foci tended to be present in cirrhotic livers, but it was not associated wi th the grade of inflammatory activity of the liver. Hyperplastic foci may represent an important predictor of recurrence after hepatic resec tion.