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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1997 Oct;88(10):965–970. doi: 10.1111/j.1349-7006.1997.tb00316.x

Significant Correlation of Telomerase Activity in Thyroid Papillary Carcinomas with Cell Differentiation, Proliferation and Extrathyroidal Extension

Isao Okayasu 1,, Toji Osakabe 2, Mutsunori Fujiwara 3, Hiroki Fukuda 4, Motonobu Kato 4, Mitsuo Oshimura 4
PMCID: PMC5921284  PMID: 9414658

Abstract

Telomerase activity was examined by telomeric repeat amplification protocol assay in thyroid disease states, including adenomas and carcinomas, and correlated with clinicopathological features. Of a total of 26 papillary carcinomas, 16 cases (61.5%) were positive, with the poorly differentiated subtype being predominant (P<0.05). A significantly more shortened terminal restriction fragment length (P<0.05), higher incidence of extrathyroidal extension (P< 0.001), and more elevated Ki‐67 labeling indices (P<0.002) were also found in telomerase‐positive than in telomerase‐negative papillary carcinomas. Of four follicular carcinomas, 3 cases (75.0%) were positive. Positive telomerase activity in follicular adenomas (9/23 cases, 39.1%) and lymphocytic thyroiditis (12/22 cases, 54.5%) appeared to be mainly caused by infiltrating lymphocytes. However, three cases of atypical adenoma with relatively increased Ki‐67 labeling indices were positive, suggesting a possibility of malignant potential. The good correlations with extrathyroidal invasiveness, Ki‐67 labeling indices and poor differentiation of papillary carcinomas, established by multivariatc analysis, suggest that this parameter might have potential application in the estimation of tumor progession and prognosis, and in clinical management

Keywords: Telomerase, Papillary carcinoma, Ki‐67, Differentiation, Thyroid carcinoma

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REFERENCES

  • 1. ) Hiyama , E. , Yokoyama , T. , Tatsumoto , N.Hiyama , K. , Imamura , Y. , Murakami , Y. , Kodama , T. , Piatyszek , M. A. , Shay , J. W. and Matsuura , Y.Telomerase activity in gastric cancer . Cancer Res. , 55 , 3258 – 3262 ( 1995. ). [PubMed] [Google Scholar]
  • 2. ) Chadeneau , C. , Hay , K. , Hirte , H. W. , Gallinger , S. and Bacchetti , S.Telomerase activity associated with acquisition of malignancy in human colorectal cancer . Cancer Res. , 55 , 2533 – 2536 ( 1995. ). [PubMed] [Google Scholar]
  • 3. ) Tahara , H. , Nakanishi , T. , Kitamoto , M. , Nakashio , R. , Shay , J. W. , Tahara , E. , Kajiyama , G. and Ide , T.Telomerase activity in human liver tissue: comparison between chronic liver disease and hepatocellular carcinomas . Cancer Res. , 55 , 2734 – 2736 ( 1995. ). [PubMed] [Google Scholar]
  • 4. ) Mehle , C. , Piatyszek , M. A. , Ljunberg , B. , Shay , J. W. and Roos , G.Telomerase activity in renal cell carcinoma . Proc. Am. Assoc. Cancer Res. , 36 , 3309 ( 1995. ) abstr . [Google Scholar]
  • 5. ) Hiyama , K. , Hiyama , E. , Ishioka , S. , Yamakido , M. , Inai , K. , Gazdar , A. F. , Piatyszek , M. A. and Shay , J. W.Telomerase activity in small‐cell and non‐small‐cell lung cancers.,7 . Natl Cancer Inst. , 87 , 895 – 902 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Langford , L. A. , Piatyszek , M. A. , Xu , R. , Schold , S. C. , Jr. and Shay , J. W.Telomerase activity in human brain tumours . Lancet , 346 , 1267 – 1268 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Kim , N. W. , Piatyszek , M. A. , Prowse , K. R. , Harley , C. B. , West , M. D. , Ho , P. L. , Coviello , G. M , Wright , W. E. , Weinrich , S. L. and Shay , J. W.Specific association of human telomerase activity with immortal cells and cancer . Science , 266 , 2011 – 2015 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Hiyama , E. , Gollahon , L. , Kataoka , T. , Kuroi , K. , Yokoyama , T. , Gazdar , A. F. , Hiyama , K. , Piatyszek , M. A. and Shay , J. W.Telomerase activity in human breast tumors . J Natl. Cancer Inst. , 88 , 116 – 122 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Landberg , G. , Nielsen , N. H. , Nilsson , P. , Emdin , S. O. , Cajander , J. and Roos , G.Telomerase activity is associated with cell cycle deregulation in human breast cancer . Cancer Res. , 57 , 549 – 554 ( 1997. ). [PubMed] [Google Scholar]
  • 10. ) Counter , C. M. , Gupta , J. , Harley , C. B. , Leber , B. and Bacchetti , S.Telomerase activity in normal leukocytes and in haematologic malignancies . Blood , 85 , 2315 – 2320 ( 1995. ). [PubMed] [Google Scholar]
  • 11. ) Umbricht , C. B , Saji , M. , Westra , W. H. , Udelsman , R. , Zeiger , M. A. and Sukumar , S.Telomerase activity: a marker to distinguish follicular thyroid adenoma from carcinoma . Cancer Res. , 57 , 2144 – 2147 ( 1997. ). [PubMed] [Google Scholar]
  • 12. ) Franssila , K. O.Prognosis in thyroid carcinoma . Cancer , 36 , 1138 – 1146 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Harwood , J. H. , Clark , O. H. and Dunphy , J. E.Significance of lymph node metastasis in differentiated thyroid cancer . Am. J. Surg. , 136 , 1107 – 1112 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Cady , B. , Sedgwick , C. E. , Meissner , W. A. , Wool , M. S. , Salzman , F. A. and Werber , J.Risk factor analysis in differentiated thyroid cancer . Cancer , 43 , 810 – 820 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Sakamoto , A. , Kasai , N. and Sugano , H.Poorly differentiated carcinoma of the thyroid. A clinicopathologic entity for a high‐risk group of papillary and follicular carcinomas . Cancer , 52 , 1849 – 1855 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Damiani , S. , Dina , R. and Eusebi , V.Cytologic grading of aggressive and nonaggressive variants of papillary thyroid carcinoma . Am. J. Clin. Pathol. , 101 , 651 – 655 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Hedinger , C. , Williams , E. D. and Sobin , L. H.Histologic typing of thyroid tumors . In “ International Histological Classification of Tumours, vol. 11 ” 2nd Ed. , World Health Organization , pp. 5 – 18 ( 1993. ). Springer‐Verlag; , Berlin . [Google Scholar]
  • 18. ) Williams , E. D. and Doniach , I.The post‐mortem incidence of focal thyroiditis . J. Pathol Bacterial , 83 , 255 – 264 ( 1962. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Wright , W. E. , Shay , J. W. and Piatyszek , M. A.Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity . Nucleic Acids Res. , 23 , 3794 – 3795 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. ) Hastie , N. D. , Dempster , M. , Dunlop , M. G. , Thompson , A. M. , Green , D. K. and Allshire , R. C.Telomere reduction in human colorectal carcinoma and with ageing . Nature , 346 , 866 – 868 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Walker , S. H. and Duncan , D. B.Estimation of the probability of an event as a function of several independent variables . Biometrika , 54 , 167 – 179 ( 1967. ). [PubMed] [Google Scholar]
  • 22. ) SAS/STAT User's Guide Version 6, Vol. 2 , 4th Ed. ( 1990. ). SAS Institute Inc. , Gary , NC . [Google Scholar]
  • 23. ) Rhyu , M. S.Telomeres, telomerase, and immortality . J. Natl Cancer Inst. , 87 , 884 – 894 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Broccoli , D. , Young , J. W. and DeLange , T.Telomerase activity in normal and malignant hematopoietic cells . Proc. Natl. Acad. Sci. USA , 92 , 9082 – 9086 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. ) Okayasu , I. , Saegusa , M. , Fujiwara , M. , Hara , Y. and Rose , N. R.Enhanced cellular proliferative activity and cell death in chronic thyroiditis and thyroid papillary carcinoma . J Cancer Res. Clin. Oncol , 121 , 746 – 752 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Gerdes , J. , Lemke , H. , Baisch , H , Wacker , H. H. , Schwabb , U. and Stein , H.Cell cycle analysis of a cell proliferation‐associated human nuclear antigen defined by the monoclonal antibody Ki‐67 . J Immunol. , 133 , 1710 – 1715 ( 1984. ). [PubMed] [Google Scholar]
  • 27. ) Hiyama , K. , Hirai , Y. , Kyoizumi , S. , Akiyama , M. , Hiyama , E. , Piatyszek , M. A. , Shay , J. W. , Ishioka , S. and Yamakido , M.Activation of telomerase in human lymphocytes and hematopoietic progenitor cells . J. Immunol , 155 , 3711 – 3715 ( 1995. ). [PubMed] [Google Scholar]
  • 28. ) Kyo , S. , Takakura , M. , Kohama , T. and Inoue , M.Telomerase activity in human endometrium . Cancer Res. , 57 , 610 – 614 ( 1997. ). [PubMed] [Google Scholar]
  • 29. ) Albanell , J. , Han , W. , Mellado , B. , Gunawardane , R. , Scher , H. I. , Dmitrovsky , E. and Moore , M. A. S.Telomerase activity is repressed during differentiation of maturation‐sensitive but not resistant human tumor cell lines . Cancer Res. , 56 , 1503 – 1508 ( 1996. ). [PubMed] [Google Scholar]
  • 30. ) Dobashi , Y. , Sakamoto , A. , Sugimura , H. , Mernyei , M. , Mori , M. , Oyama , T. and Machinami , R.Overexpression of p53 as a possible prognostic factor in human thyroid carcinoma . Am. J. Surg. Pathol. , 17 , 375 – 381 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Dobashi , Y. , Sugimura , H. , Sakamoto , A. , Mernyei , M. , Mori , M. , Oyama , T. and Machinami , R.Stepwise participation of p53 gene mutation during dedifferentiation of human thyroid carcinomas . Diag. Mol. Pathol , 3 , 9 – 14 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 32. ) Okayasu , I. , Fujiwara , M. , Hara , Y. , Tanaka , Y. and Rose , N. R.Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma . Cancer , 76 , 2312 – 2318 ( 1995. ). [DOI] [PubMed] [Google Scholar]

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