PROLIFERATING CELL NUCLEAR ANTIGEN IN HEPATOCELLULAR-CARCINOMA AND SMALL-CELL LIVER DYSPLASIA

Background. Recently, proliferating cell nuclear antigen (PCNA) has been measured by using a monoclonal antibody in a variety of malignant neoplasms. Methods. The authors evaluated cell proliferative activity by immunostaining for PCNA in 92 hepatocellular carcinoma nodules and 14 lesions of small cell liver dysplasia. Results. The average PCNA labeling indices (LI) in Grades I, II, III, and IV were 12.2%, 17.5%, 53.7%, and 83.9%, respectively. There were statistically significant differences in the PCNA LI between all the histologic grades, except for Grades I and II. The less differentiated the histologic grade, the higher the PCNA LI became. This finding was also recognized in a hepatocellular carcinoma showing a ''nodule in a nodule'' appearance, in which the less-differentiated inner nodule had a higher PCNA LI than did the well-differentiated outer lesion. For an analysis of the disease-free survival in 74 patients with clinical follow-up data, 2 groups of patients with a PCNA LI higher and lower than the average level (32.0%) were compared. The disease-free survival rate after surgery was significantly higher (P < 0.005), and the venous invasion was significantly less frequent (P = 0.0003) in the low PCNA LI group than in the high PCNA LI group. The average PCNA LI in small cell liver dysplasia was 13.9%, which was almost equal to that of Grades I and II hepatocellular carcinoma. Conclusions. The PCNA LI of hepatocellular carcinoma showed a close correlation with both the histologic findings and the biologic behavior. Small cell liver dysplasia was a small round focus having proliferative activity similar to that of Grades I and II hepatocellular carcinoma.