Abstract
Although telomerase activity in hepatocellular carcinoma (HCC) increases in accordance with degree of histological undifferentiation, it is unknown whether the level of telomerase activity in HCC reflects of the degree of activity in individual cells or the frequency of telomerase-positive HCC cells. Non-cancerous liver tissues exhibit low but significant levels of telomerase 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 hTERT-positive hepatocytes, though very low frequency, in non-cancerous liver tissues. The frequencies in hTERT positive hepatocytes were very well correlated 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 poorly differentiated HCC 95%. The intensity of staining varied among cells within a given specimen, and correlation with degree of histological undifferentiation was less obvious. Portions of migrating lymphocytes and biliary epithelial cells were also hTERT-positive. These findings indicate that the up-regulation of telomerase activity with degree of undifferentiation of HCC is mainly due to the increase in frequency of hTERT positive HCC cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Baumann U, Crosby HA, Ramani P, Kelly DA and Strain AJ. . 1999 Hepatology 30: 112–117.
Blackburn EH. . 1991 Nature 350: 569–573.
Blackburn EH. . 1992 Annu. Rev. Biochem. 61: 113–129.
Blackburn EH and Szostak JW. . 1984 Annu. Rev. Biochem. 53: 163–194.
Counter CM, Avilion AA, Lefeuvre CE, Stewart NG, Greider CW, Harley CB and Bacchetti S. . 1992 EMBO J. 11: 1921–1929.
Crosby HA, Hubscher SG, Joplin RE, Kelly DA and Strain AJ. . 1998a Hepatology 28: 980–985.
Crosby HA, Hubscher S, Fabris L, Joplin R, Sell S, Kelly D and Strain AJ. . 1998b Am. J. Pathol. 152: 771–779.
De Vos R and Desmet V. . 1992 Am. J. Pathol. 140: 1441–1450.
Demetris AJ, Seaberg EC, Wennerberg A, Ionellie J and Michalopoulos G. . 1996 Am. J. Pathol. 149: 439–448.
Dunsford HA, Karnasuta C, Hunt JM and Sell S. . 1989 Cancer Res. 49: 4894–4900.
Dunsford HA, Maset R, Salman J and Sell S. . 1985 Am. J. Pathol. 118: 218–224.
Edmondson HA and Steiner PE. . 1954 Cancer 7: 462–503.
Elmore LW and Sirica AE. . 1991 Cancer Res. 51: 5752–5759.
Evarts RP, Nagy P, Nakatsukasa H, Marsden E and Thorgeirsson SS. . 1989 Cancer Res. 49: 1541–1547.
Golding M, Sarraf CE, Lalani E, Anilkumar TV, Edwards RJ, Nagy P, Thorgeirsson SS and Alison MR. . 1995 Hepatology 22: 1243–1253.
Greider CW. . 1998 Proc. Natl. Acad. Sci. USA 95: 90–92.
Haque S, Haruna Y, Saito K, Nalesnik MA, Atillasoy E, Thung SN and Gerber MA. . 1996 Lab. Invest. 75: 699–705.
Harley CB. . 1991 Mutat. Res. 256: 271–282.
Kawakita N, Seki S, Sakaguchi H, Yanai A, Kuroki T, Mizoguchi Y, Kobayashi K and Monna T. . 1992 Am. J. Pathol. 140: 513–520.
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL and Shay JW. . 1994 Science 266: 2011–2015.
Kolquist KA, Ellisen LW, Counter CM, Meyerson M, Tan LK, Weinberg RA, Haber DA and Gerald WL. . 1998 Nat. Genet. 19: 182–186.
Nakamura Y, Tahara Eg, Tahara H, Yasui W, Tahara E and Ide T. . 1999 Mol. Carcinog. 26: 312–320.
Nakashio R, Kitamoto M, Tahara H, Nakanishi T, Ide T and Kajiyama G. . 1997 Int. J. Cancer 74: 141–147.
Nakayama J, Tahara H, Tahara Eg, Saito M, Ito K, Nakamura H, Nakanishi T, Tahara E, Ide T and Ishikawa F. . 1998 Nat. Genet. 18: 65–68.
Novikoff PM, Yam A and Oikawa I. . 1996 Am. J. Pathol. 148: 1473–1492.
Ogami M, Ikura Y, Nishiguchi S, Kuroki T, Ueda M and Sakurai M. . 1999 Lab. Invest. 79: 15–26.
Ohyashiki K, Ohyashiki JH, Nishimaki J, Toyama K, Ebihara Y, Kato H, Wright WE and Shay JW. . 1997 Cancer Res. 57: 2100–2103.
Ouellette MM, Aisner DL, Savre-train I, Wright WE and Shay JW. . 1999 Biochem. Biophys. Res. Commun. 254: 795–803.
Roskams T, De Vos R and Desmet V. . 1996 Histopathology 28: 291–299.
Ruck P, Xiao JC and Kaiserling E. . 1996 Am. J. Pathol. 148: 321–329.
Seki S, Sakaguchi H, Kawakita N, Yanai A, Kim K, Mizoguchi Y and Kobayashi K. . 1990 Human Pathol. 21: 1020–1030.
Seki S, Sakaguchi H, Kawakita N, Yanai A, Kuroki T, Mizoguchi Y, Kobayashi K and Monna T. . 1991 Hepatology 14: 781–788.
Tahara H, Nakanishi T, Kitamoto M, Nakashio R, Shay JW, Tahara E, Kajiyama G and Ide T. . 1995 Cancer Res. 55: 2734–2736.
Tahara H, Yasui W, Tahara EJ, Fujimoto J, Ito K, Tamai K, Nakayama J, Ishikawa F, Tahara E and Ide T. . 1999 Oncogene 18: 1561–1567.
Takahashi S, Kitamoto M, Takaishi H, Aikata H, Kawakami Y, Nakanishi T, Shimamoto F, Tahara E, Tahara H, Ide T and Kajiyama G. . 2000 Euro. J. Cancer 36: 496–502.
Takaishi H, Kitamoto M, Takahashi S, Aikata H, Kawakami Y, Nakanishi T, Nakamura Y, Shimamoto F, Kajiyama G and Ide T. . 2000 Cancer 88: 312–317.
Weng NP, Hathcock KS and Hodes RJ. . 1998 Immunity. 9: 151–157.
Yasui W, Akama Y, Kuniyasu H, Yokozaki H, Semba S, Shimamoto F and Tahara E. . 1996 J. Pathol. 180: 122–128.
Yasui W, Tahara H, Tahara EJ, Fujimoto J, Nakayama J, Ishikawa F, Ide T and Tahara E. . 1998 Jpn. J. Cancer Res. 89: 1099–1103.
Yasui W, Tahara EJ, Tahara H, Fujimoto J, Naka K, Nakayama J, Ishikawa F, Ide T and Tahara E. . 1999 Jpn. J. Cancer Res. 90: 589–595.
Zakian VA. . 1989 Annu. Rev. Genet. 23: 579–604.
Acknowledgements
The authors thank Dr T Asahara (Second Department of Surgery, Hiroshima University School of Medicine) for providing tissue specimens.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kawakami, Y., Kitamoto, M., Nakanishi, T. et al. Immuno-histochemical detection of human telomerase reverse transcriptase in human liver tissues. Oncogene 19, 3888–3893 (2000). https://doi.org/10.1038/sj.onc.1203733
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203733
Keywords
This article is cited by
-
HCV core inhibits hepatocellular carcinoma cell replicative senescence through downregulating microRNA-138 expression
Journal of Molecular Medicine (2017)
-
Nuclear telomerase is less accessible to antibody probing than known nuclear antigens: retrieval with new immunostaining buffer
Histochemistry and Cell Biology (2005)
-
Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours
British Journal of Cancer (2004)
-
Telomerase-dependent oncolytic adenovirus for cancer treatment
Gene Therapy (2003)
-
hTERT associates with human telomeres and enhances genomic stability and DNA repair
Oncogene (2003)