In situ detection of telomerase enzymatic activity in human hepatocellular carcinogenesis
Article first published online: 5 JUL 2001
Copyright © 2001 John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 194, Issue 4, pages 459–465, August 2001
How to Cite
Youssef, N., Paradis, V., Ferlicot, S. and Bedossa, P. (2001), In situ detection of telomerase enzymatic activity in human hepatocellular carcinogenesis. J. Pathol., 194: 459–465. doi: 10.1002/path.901
- Issue published online: 15 AUG 2001
- Article first published online: 5 JUL 2001
- Manuscript Accepted: 30 JAN 2001
- Manuscript Revised: 13 DEC 2000
- Manuscript Received: 30 AUG 2000
- hepatocellular carcinoma;
- chronic hepatitis
Telomerase enzymatic activity has been detected in most human malignant tumours including hepatocellular carcinoma. In order to assess the cellular source, the topographic distribution, and the chronology of telomerase re-expression during human liver carcinogenesis, an in situ technique derived from the standard TRAP (telomeric repeat amplification protocol) assay was set up that allowed the detection of telomerase enzyme activity at the cellular level on frozen liver tissue sections. In situ TRAP (ISTRAP) was performed on 27 hepatocellular carcinomas (HCCs) and 57 non-tumour livers, including normal liver without HCC, liver samples adjacent to tumour with and without hepatic cirrhosis, and biopsies of chronic hepatitis. In HCC, telomerase was detected in the nuclei of liver tumour cells in 23/27 cases (85%), with a heterogeneous distribution within the tumour. This signal was also detected in clusters of hepatocytes in 16/26 (61%) samples of liver adjacent to HCC, in 10/23 (43%) cases of chronic viral hepatitis without adjacent HCC, and in scattered nuclei of 2/8 histologically normal livers. Comparison of the results obtained with ISTRAP and standard TRAP assays on tissue extracts suggests a gain in sensitivity with the in situ technique. This study confirms that telomerase is expressed in most HCCs and suggests that focal telomerase reactivation is an early event during human liver carcinogenesis. ISTRAP is a sensitive technique that allows the study of telomerase expression in the morphological context. Copyright © 2001 John Wiley & Sons, Ltd.