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.

Precise diagnosis of well-differentiated hepatocellular carcinoma (HCC) is sometimes difficult to establish. Telomerase activity was examined by telomeric-repeat-amplification protocol (TRAP) in 37 HCC nodules smaller than 3 cm in diameter, including 24 fine-needle-aspiration biopsy specimens, 22 non-tumor chronic-liver-disease tissues (9 chronic hepatitis and 13 liver cirrhosis) and 3 normal liver tissues. Telomerase activity was assayed by serially diluted samples and quantitated by using an internal telomerase assay standard (ITAS). Telomerase activity was detected in all HCC and in 11 of 22 non-tumor chronic-liver-disease tissues. Normal liver samples had undetectable telomerase activity. Cut-off level of telomerase activity for its practical usage in HCC diagnosis was tentatively set for 0.6 mg liver protein/ assay at 10-cell equivalent activity of a gastric-cancer cell line, MKN-1. This level was twice the highest activity in non-tumor chronic liver disease therefore, telomerase activity in all non-tumor liver samples was below this level. The telomerasepositive incidence exceeding this cut-off level was 73% (11/15) in well-differentiated HCC, 94% (16/17) in moderately differentiated HCC and 100% (5/5) in poorly differentiated HCC. Well-differentiated HCC showed low positivity by other diagnostic markers. 21% by AFP, 0% by PIVKA-II and 13% by angiography. The detection of telomerase activity may thus be a useful additional tool for precise and early diagnosis of small differentiated HCC, even when diagnosis is inconclusive by conventional techniques. Int.

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