Skip to main content

Advertisement

Log in

Telomerase activity in hepatocellular carcinoma as a predictor of postoperative recurrence

  • Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Telomerase is a ribonucleoprotein that stabilizes telomeres and allows unlimited cell division. It has been reported that most cancer cells evince reactivated telomerase. We examined telomerase activity in 29 patients with hepatocellular carcinoma (HCC) by a polymerase chain reaction-based semiquantitative assay. Of 24 HCCs, telomerase activity was positive in 23 (95,8%), of which 16 showed strong activity. In 11 well differentiated HCCs, telomerase activity was strong in 5, weak in 5, and undetected in 1 and in 13 moderately differentiated HCCs, it was strong in 11 and weak in 2. Five of 6 HCCs less than 2 cm in diameter expressed strong telomerase activity, while weak telomerase activity was detected in 7 of 19 (36.8%) resected noncancerous liver tissues from the HCC patients. Five of these 7 patients (71%) manifested recurrence within 6 months after surgery. The recurrence rate in these patients whose noncancerous liver tissue was positive for telomerase activity was significantly higher than that in patients in whom it was negative (P=0.017). These results suggest that the presence of telomerase activity may be a useful diagnostic marker of HCC, regardless of tumor size, and that its detection in resected noncancerous liver tissues may serve as a useful predictor of postoperative recurrence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965;37:614–636.

    Article  PubMed  CAS  Google Scholar 

  2. Harley CB, Futcher AB, Greider CW. Telomeres shorten during aging of human fibroblasts. Nature 1990;345:458–460.

    Article  PubMed  CAS  Google Scholar 

  3. Lindsey J, McGill NI, Lindsey LA, et al. In vivo loss of telomeric repeats with age in humans. Mutat Res 1991;256:45–48.

    PubMed  CAS  Google Scholar 

  4. Allsopp RC, Vaziri H, Petterson C, et al. Tolomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 1992;89:10114–10118.

    Article  PubMed  CAS  Google Scholar 

  5. Morin GB. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 1989;59:521–529.

    Article  PubMed  CAS  Google Scholar 

  6. Counter CM, Avilion AA, LeFeuvre CE, et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 1992;11:1921–1929.

    PubMed  CAS  Google Scholar 

  7. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994;266:2011–2015.

    Article  PubMed  CAS  Google Scholar 

  8. Harley CB, Vaziri H, Counter CM, et al. The telomere hypothesis of cellular aging. Exp Gerontol 1992;27:375–382.

    Article  PubMed  CAS  Google Scholar 

  9. Counter CM, Hirte HW, Bacchetti S, et al. Telomerase activity in human ovarian carcinoma. Proc Natl Acad Sci USA 1994;91: 2900–2904.

    Article  PubMed  CAS  Google Scholar 

  10. Tahara H, Nakanishi T, Kitamoto M, et al. Telomerase activity in human liver tissues: Comparison between chronic liver disease and hepatocellular carcinoma. Cancer Res 1995;55:2734–2736.

    PubMed  CAS  Google Scholar 

  11. Nouso K., Urabe Y, Higashi T, et al. Telomerase as a tool for the differential diagnosis of human hepatocellular carcinoma. Cancer 1996;78:232–236.

    Article  PubMed  CAS  Google Scholar 

  12. Kojima H, Yokosuka O, Imazeki F, et al. Telomerase activity and telomere length in hepatocellular carcinoma and chronic liver disease. Gastroenterology 1997; 112:493–500.

    Article  PubMed  CAS  Google Scholar 

  13. Chadeneau C, Hay K, Hirte HW, et al. Telomerase activity associated with acquisition of malignancy in human colorectal cancer. Cancer Res 1995;55:2533–2536.

    PubMed  CAS  Google Scholar 

  14. Hiyama E, Yokoyama T, Tatsumoto N, et al. Telomerase activity in gastric cancer. Cancer Res 1995;55:3258–2362.

    PubMed  CAS  Google Scholar 

  15. Hiyama E, Kodama T, Shinbara K, et al. Felomerase activity is detected in pancreatic cancer but not in benign tumors. Cancer Res 1997;57:326–331.

    PubMed  CAS  Google Scholar 

  16. Sugawara K and Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary liver cancer (in Japanese). Tokyo: Kanehara Shuppan, 1992.

    Google Scholar 

  17. De Groote J, Desmet VJ, Gedigk P, et al. A classification of chronic hepatitis. Lancet 1968;2:626–628.

    PubMed  Google Scholar 

  18. Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431–435.

    Article  PubMed  CAS  Google Scholar 

  19. Ohyashiki JH, Ohyashiki K, Sano T, et al. Non-radioisotopic and semi-quantitative procedure for terminal repeat amplification protocol. Jpn J Cancer Res 1996;87:329–331.

    PubMed  CAS  Google Scholar 

  20. Kenmochi K, Sugihara S, Kojiro M. Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells multiple different grades in single small HCC. Liver 1987;7:18–26.

    PubMed  CAS  Google Scholar 

  21. Nishioka K, Watanabe J, Furuta S, et al. A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan. Cancer 1991;67:429–433.

    Article  PubMed  CAS  Google Scholar 

  22. Ohashi K, Tsutsumi M, Nakajima Y, et al. Telomere changes in human hepatocellular carcinomas and hepatitis virus-infected noncancerous livers. Cancer 1996;67;1747–1751.

    Google Scholar 

  23. Counter CM, Gupta J, Harley CB, et al. Telomerase activity in normal leukocytes and in hematologic malignancies. Blood 1995;85:2315–2320.

    PubMed  CAS  Google Scholar 

  24. Vauthey JN, Klimstra D, Franceschi D, et al. Factors affecting long-term outcome after hepatic resection for hepatocellular carcinoma. Am J Surg 1995;169:28–34.

    Article  PubMed  CAS  Google Scholar 

  25. Arii S, Tanaka J, Yamazoe Y, et al. Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy. Cancer 1992;69:913–919.

    Article  PubMed  CAS  Google Scholar 

  26. Nagashima I, Hamada C, Naruse K, et al. Surgical resection for small hepatocellular carcinoma. Surgery 1996;119:40–45.

    Article  PubMed  CAS  Google Scholar 

  27. Kar S, Carr BI. Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma. Hepatology 1995;21:403–407.

    PubMed  CAS  Google Scholar 

  28. Matsumura M, Niwa Y, Koto N, et al. Detection of α-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: A possible predictor of metastatic hepatocellular carcinoma. Hepatology 1994;20: 1418–1425.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ohta, K., Kanamaru, T., Morita, Y. et al. Telomerase activity in hepatocellular carcinoma as a predictor of postoperative recurrence. J Gastroenterol 32, 791–796 (1997). https://doi.org/10.1007/BF02936956

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02936956

Key words

Navigation