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-gamma-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 alpha-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%).


CONCLUSIONS
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-gamma-carboxy prothrombin and an earlier recurrence after hepatectomy than that of HCC with a low telomerase activity.
Shimada
M
M
Second Department of Surgery, Faculty of Medicine, Kyushu University, Kyushu University Hospital, Fukuoka, Japan.
Hasegawa
H
H
Gion
T
T
Utsunomiya
T
T
Shirabe
K
K
Takenaka
K
K
Otsuka
T
T
Maehara
Y
Y
Sugimachi
K
K
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D019098:Telomerase / Q000502:physiology*
D015415:Biomarkers; D011498:Protein Precursors; C008208:acarboxyprothrombin; D011516:Prothrombin; D019098:Telomerase