The assessment of proliferating cell nuclear antigen immunohistochemical staining in small hepatocellular carcinoma and its relationship to histologic characteristics and prognosis

Background. A precise prognostic factor for small hepatocellular carcinoma (HCC), the diagnosis of which recently has increased in incidence because of the development of diagnostic imaging techniques, is desirable. It has been reported that proliferating cell nuclear antigen (PCNA) would be related to proliferating cells, and thus the PCNA labeling index may provide useful information about the biologic behavior of small HCC. Methods. An assessment was made of proliferative activity by immunohistochemical staining using a monoclonal antibody against PCNA in 46 nodules of HCC less than 3 cm in diameter resected from 44 patients. A correlation between PCNA labeling index and clinicopathologic findings or prognosis was sought. Results. The mean labeling index was 18.7% in HCC and 1.9% in nontumor liver tissue. The labeling index corresponded to the degree of histologic differentiation, and the labeling index of well differentiated HCC was significantly lower (P < 0.05) than that of moderately or poorly differentiated HCC. The incidence of capsule formation in the high labeling index group (labeling index ± 20%) was significantly higher (P < 0.05) than that in the low labeling index group (labeling index < 20%). A high incidence of capsular and vascular invasion was found in the high labeling index group. The survival rate after resection was significantly higher (P < 0.05) and the recurrence rate significantly lower (P < 0.05) in the low labeling index group than in the high labeling index group. Conclusions. The PCNA labeling index was shown to be closely related to histologic characteristics, and proved to be a useful indicator of recurrence and survival in small HCC.