Immuno-histochemical detection of human telomerase reverse transcriptase in human liver tissues

Although telomerase activity in hepatocellular carcinoma (HCC) increases in accordance with degree of histological undifferentiation, it is unknown wh ether the level of telomerase activity in HCC reflects of the degree of act ivity in individual cells or the frequency of telomerase-positive HCC cells . Non-cancerous liver tissues exhibit low but significant levels of telomer ase activity, but the nature of telomerase-positive cells in these tissues is unclear, In this study, we performed immunohistochemical staining using specific antibody against telomerase reverse transcriptase (hTERT) protein in 15 HCC samples and 13 adjacent non-cancerous liver tissues, There were h TERT-positive hepatocytes, though very low frequency, in non-cancerous live r tissues. The frequencies in hTERT positive hepatocytes were very well cor related with clinicopathological parameters and telomerase activity levels: the average frequencies of chronic hepatitis was 0.2%, liver cirrhosis 0.2 %, well-differentiated HCC 3.0%, moderately differentiated HCC 28%, and poo rly differentiated HCC 95%, The intensity of staining varied among cells wi thin a given specimen, and correlation with degree of histological undiffer entiation was less obvious. Portions of migrating lymphocytes and biliary e pithelial cells were also hTERT-positive. These findings indicate that the upregulation of telomerase activity with degree of undifferentiation of HCC is mainly due to the increase in frequency of hTERT positive HCC cells.