Scientific paper
Telomerase activity as a predictive marker for recurrence of hepatocellular carcinoma after hepatectomy

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Abstract

Background: Expression of telomerase activity and stabilization of telomeres are concomitant with attainment of immortality in tumor cells. Telomerase activity levels in hepatocellular carcinoma (HCC) may serve as a predictive marker for recurrence after surgery.

Methods: Telomerase activity levels in HCC were measured in 37 patients undergoing hepatectomy by the telomeric repeat amplification protocol. The clinicopathologic factors and telomerase activity were analyzed to identify factors that were important in affecting recurrence of HCC and recurrence-free survival.

Results: Telomerase activity was detected in 23 patients (62.2%), and was not significantly associated with seven other HCC-related factors. After a median follow-up of 34 months, 24 patients (64.9%) had recurrence of HCC. In univariate analyses, telomerase activity of more than 20 total product generated (TPG) and portal vein invasion were found to be significantly related to a shorter time to recurrence. Multivariate analysis demonstrated that telomerase activity (>20 TPG) was significantly related to an increased risk of recurrence (relative risk 2.36, 95% confidence interval 1.03 to 5.43, P = 0.04).

Conclusions: Telomerase activity can be identified as an independent predictor for recurrence after resection of HCC.

Section snippets

Methods

Thirty-seven consecutive patients who underwent curative resection for HCC from September 1996 to September 1997 were investigated prospectively. Among 37 patients (31 men and 6 women; median age 63 years, range 43 to 79), 11 had chronic hepatitis, 22 had liver cirrhosis, and 4 had liver fibrosis. Anatomical resection included hepatic lobectomy, segmentectomy, and subsegmentectomy; and nonatomical resection was defined as a limited resection of smaller part of the subsegment. After surgery, all

Results

Telomerase activity in HCC was detected in 23 of 37 specimens (62.2%). Telomerase activity levels were not significantly associated with tumor cell differentiation, capsule formation, portal vein invasion, intrahepatic metastasis, TNM clinical stage, tumor size, or serum alpha-fetoprotein level (Table 1).

During a median follow-up of 34 months (range 28 to 44), HCC recurred in 24 of 37 patients (64.9%). The 1-year, 2-year, and 3-year recurrence-free survival rates were 56.8%, 51.4%, and 31.5%,

Comments

Telomerase activity was detected in 23 of 37 HCC specimens (62.2%). Previous series have reported widely disparate telomerase positive rates for HCC, ranging from 61.5% to 100% [7], [9], [11], [16]. In the present study, telomerase activity was observed in all stages of HCC, supporting the hypothesis that telomerase reactivation may be an early event in the malignant progression of HCC [17], whereas it is known to occur at a later stage in other carcinomas [18]. The correlation among telomerase

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