Quantitation of telomerase activity in hepatocellular carcinoma: A possible aid for a prediction of recurrent diseases in the remnant liver

Abstract

Because telomerase activity is necessary for cell immortality and probably associated with tumor progression, we have evaluated a possible aid for quantitation of the activity to predict intrahepatic recurrences after surgery in patients with hepatocellular carcinoma (HCC). HCC tissues obtained by surgical resection from 20 patients were studied. Telomerase activity was expressed as peaks with a periodicity through a fluorescence-based telomeric repeat amplification protocol using an autosequencer, and the quantity of activity was calculated from peak areas. A ratio of fluorescence intensity depending on telomerase to that of an internal standard was used as a value of relative telomerase activity (RTA). RTA in serially diluted S100 extracts from HepG2 cells was well correlated with the amount of the extracts. The mean RTA value of 36.4 ؎ 27.8 (mean ؎ SD, 3.21 to 105) in 9 patients suffering from early recurrences after surgery was significantly higher than that (9.84 ؎ 7.65; mean ؎ SD, 3.00 to 29.0) in 11 patients without intrahepatic recurrences during the early period (P ‫؍‬ .004). These results indicate that RTA value can be a useful predictor for intrahepatic recurrences during the early period after surgical resection of HCC. (HEPATOLOGY 1998; 27:402-406.)

High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis

“…[31][32][33] In our study, the difference in overall survival according to hTERT mRNA levels failed to reach statistical significance, unlike previous studies which showed that high hTERT expression was associated with a poorer prognosis in colorectal carcinomas and ependymomas. 34,35 However, we found that high hTERT mRNA levels were significantly correlated with more advanced tumor stage.…”

Reduction of telomeric repeats as a possible predictor for development of hepatocellular carcinoma: Convenient evaluation by slot-blot analysis

“…[19][20][21][22] Unfortunately, however, no information could be provided for a risk of de novo HCC development by quantification of telomerase activity, because the activity is seldom detected in noncancerous liver tissues. On the other hand, it seems to be relevant to assume that the extent of telomere reduction can be a predictor for multicentric carcinogenesis in chronic liver diseases, because persistent hepatocellular degeneration seems to play a key role in hepatocarcinogenesis, 2 and telomere reduction may indicate replicative history of hepatocyte.…”

The reduction of cell death and proliferation by p27Kip1 minimizes DNA damage in an experimental model of genotoxicity

“…8 The molecular changes correlated with recurrence or metastasis of HCC would be useful to screen patients with high risk of recurrence. 4,9,10 Although many biomarkers have been tried, such as a-fetoprotein (AFP) mRNA, circulating VEGF and PD-ECGF, human macrophage metalloelastase gene, 11 p27, 12 p53 mutation, 9 p73 expression, 13 telomerase activity, 14 etc., a routine biomarker for prediction of metastasis and recurrence is not yet available.…”