High expression of telomerase is an independent prognostic indicator of poor outcome in hepatoblastoma.
Telomerase, an enzyme related with cellular immortality, has been extensively studied in many kinds of malignant tumours for clinical diagnostic or prognostic utilities. Telomerase activity is mainly regulated by the expression of hTERT (human telomerase reverse transcriptase), which is a catalytic component of human telomerase. To evaluate whether the levels of hTERT mRNA provides a molecular marker of hepatoblastoma malignancy, we examined hTERT mRNA expression levels in the primary hepatoblastoma tissues by fluorescent RT-PCR using LightCycler technology and followed up the clinical outcomes in 63 patients listed in the Japanese Study Group of Pediatric Liver Tumor between 1991 and 2002. The hTERT mRNA expression was detected in 61 (96.8%) specimens and their expression levels ranged between 0.1/1000 and 745.1/1000 copies of PBGD gene that was used as an internal control. Among these cases, frozen 39 tumour samples and 14 adjacent noncancerous liver tissues were analysed for semiquantitative telomerase assay. In the 39 tumour samples, the levels of telomerase activity ranged between 0.11 and 2709 TPG and 12 (30.7%) had high telomerase activity (>100 TPG), whereas only nine of 14 noncancerous liver tissue samples showed telomerase activity which was less than 1.0 TPG. The levels of telomerase activity were significantly correlated with the levels of hTERT mRNA expression (P<0.001). The frequency of high hTERT mRNA expression and/or high telomerase activity did not significantly associate with the clinicopathological factors except for stage of disease. The prognosis of the patients with high hTERT mRNA expression was significantly worse than that of others (P<0.01), as was the patients with high telomerase activity (P<0.01). Multivariate analysis indicated that high levels of hTERT mRNA expression as well as telomerase activity are independent prognosis-predicting factors in patients with hepatoblastoma.
Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan. eiso@hiroshima-u.ac.jp
E
E
Hiyama
H
H
Yamaoka
T
T
Matsunaga
Y
Y
Hayashi
H
H
Ando
S
S
Suita
H
H
Horie
M
M
Kaneko
F
F
Sasaki
K
K
Hashizume
A
A
Nakagawara
N
N
Ohnuma
T
T
Yokoyama
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins; D005260:Female; D018197:Hepatoblastoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase