The role of telomerase activity in hepatocellular carcinoma

OBJECTIVE: The aim of this study was to clarify the role of telomerase acti vity 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 lapar otomy. Telomerase activity was determined using a telomeric repeat amplific ation 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 defin ed as a low telomerase group. in noncancerous liver, 2+ or more of telomera se activity was defined as an increased telomerase group, and 1+ or less of telomerase activity was defined as a nonincreased telomerase group. The co rrelation between telomerase activity in HCC or noncancerous Liver and clin icopathological factors, including prognosis, was investigated. RESULTS: Telomerase activities in HCCs were 0 in one patient, if in two, 2 in seven, and 3+ in 29 patients. The disease-free survival rate in the hig h telomerase group was significantly worse than that in the low telomerase group. The des-gamma-carboxy prothrombin level in a high telomerase group ( median, 330 mAU/ml) was significantly higher than that in the low telomeras e group (median, 150 mAU/ml). A multivariate analysis revealed that higher TNM stage, high telomerase activity in HCC, female gender, and high alpha-f etoprotein value were independent significant factors related to be early r ecurrence. The incidence of multicentric HCC occurrence in the increased te lomerase group (53.3%) tended to be higher than that in the nonincreased te lomerase 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 d es-gamma-carboxy prothrombin and an earlier recurrence after hepatectomy th an that of HCC with a low telomerase activity. (Am J Gastroenterol 2000,95: 748-752. (C) 2000 by Am. Coll. of Gastroenterology).