The role of telomerase activity in hepatocellular carcinoma

OBJECTIVE: The aim of this study was to clarify the role of telomerase activity in hepatocellular carcinoma (HCC). METHODS: Specimens from both HCC and noncancerous liver were obtained from 39 patients with HCC using a 14- gauge biopsy needle immediately after laparotomy. Telomerase activity was determined using a telomeric repeat amplification protocol assay. The 3+ of telomerase activity in HCC was defined as a high telomerase group, and 2+ or less of HCC telomerase activity was defined as a low telomerase group. In noncancerous liver, 2+ or more of telomerase activity was defined as an increased telomerase group, and 1 + or less of telomerase activity was defined as a nonincreased telomerase group. The correlation between telomerase activity in HCC or noncancerous liver and clinicopathological factors, including prognosis, was investigated. RESULTS: Telomerase activities in HCCs were 0 in one patient, 1+ in two, 2+ in seven, and 3+ in 29 patients. The disease-free survival rate in the high telomerase group was significantly worse than that in the low telomerase group. The des-γ-carboxy prothrombin level in a high telomerase group (median, 330 mAU/ml) was significantly higher than that in the low telomerase group (median, 150 mAU/ml). A multivariate analysis revealed that higher TNM stage, high telomerase activity in HCC, female gender, and high α-fetoprotein value were independent significant factors related to be early recurrence. The incidence of multicentric HCC occurrence in the increased telomerase group (53.3%) tended to be higher than that in the nonincreased telomerase group (27.3%). CONCLUSION: A high telomerase activity in HCC correlated with the potential of HCC to be more malignant, which was expressed as both a high level of des- γ-carboxy prothrombin and an earlier recurrence after hepatectomy than that of HCC with a low telomerase activity. (C) 2000 by Am. Coll. of Gastroenterology.