Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Sep;85(9):939–945. doi: 10.1111/j.1349-7006.1994.tb02972.x

Apoptotic Cell Death in Human Gastric Carcinoma: Analysis by Terminal Deoxynucleotidyl Transferase‐mediated dUTP‐biotin Nick End Labeling

Noriko Kasagi 1,, Yoshihito Gomyo 1, Hiroyuki Shirai 1, Shunichi Tsujitani 2, Hisao Ito 1
PMCID: PMC5919598  PMID: 7961123

Abstract

We have examined the occurrence of apoptotic cell death in formalin‐fixed, paraffin‐embedded human gastric carcinoma specimens by the terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP‐biotin nick end labeling (TUNEL) method. The specificity of the TUNEL signals was confirmed by the omission of either TdT or biotinylated dUTP as negative controls, and by pretreatment with DNase I as a positive control. Careful observation of routine hematoxylin and eosin‐stained sections showed a few tumor cells with apoptosis, especially in well‐differentiated carcinomas. Intense TUNEL signals were frequently observed even in ordinary, non‐pyknotic nuclei of tumor cells, and occasionally also in nuclear fragments corresponding to apoptotic bodies. Apoptotic indices (number of apoptotic cells/total number of tumor cells) ranged between 7.7 and 14.5% (mean, 10.9%) in nine well‐differentiated carcinomas and between 2.7 and 7.5% (mean, 4.0%) in five which were poorly differentiated, the mean number being significantly higher in the former (P<0.01). No apparent correlation was found between apoptosis and the expression of proliferating cell nuclear antigen, P53 or Ley in the present study. This high frequency of apoptosis, implying cell loss, may be related to the slow‐growing nature of well‐differentiated carcinomas. Poorly differentiated carcinomas, including scirrhous gastric carcinomas, showed a lower incidence of apoptosis, indicating the existence of an escape mechanism from the process.

Keywords: Apoptosis, Gastric cancer, In situ end‐labeling

Full Text

The Full Text of this article is available as a PDF (869.4 KB).

REFERENCES

  • 1. ) Kerr , J. F. R. , Wyllie , A. H. and Currie , A. R.Apoptosis: a basic biological phenomenon with wide‐ranging implications in tissue kinetics . Br. J. Cancer , 26 , 239 – 257 ( 1972. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. ) Wyllie , A. H.Cell death: a new classification separating apoptosis from necrosis . In“Cell Death in Biology and Pathology,” ed. Bo wen I. D. and Lockshin R. A. , pp. 9 – 34 ( 1981. ). Chapman and Hall; , London . [Google Scholar]
  • 3. ) Umansky , S. R.The genetic program of cell death. Hypothesis and some applications: transformation, carcinogenesis, ageing . J Theor. Biol. , 97 , 591 – 602 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Brusch , W. , Kleine , L. and Tennis wood , M.The biochemistry of cell death by apoptosis . Biochem. Cell Biol. , 68 , 1071 – 1074 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Bursch , W. , Paffe , S. , Putz , B. , Barthel , G. and Schulte‐Hermann , R.Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats . Carcinogenesis , 11 , 847 – 853 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Ucker , D. S.Death by suicide: one way to go in mammalian cellular development ? New Biol. , 3 , 103 – 109 ( 1991. ). [PubMed] [Google Scholar]
  • 7. ) Kerr , J. F. R. , Searle , J. , Harmon , B. V. and Bishop , C. J.Apoptosis . In“Perspectives on Mammalian Cell Death,” ed. Potten C. S. , pp. 93 – 128 ( 1987. ). Oxford University Press; , Oxford . [Google Scholar]
  • 8. ) Martz , E. and Ho Well , D. M.CTL: virus control cells first and cytolytic cells second ? Immunol. Today , 10 , 79 – 86 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Williams , G. T.Programmed cell death: apoptosis and oncogenesis . Cell , 65 , 1097 – 1098 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Wyllie , A. H. , Morris , R. G. , Smith , A. L. and Dunlop , D.Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macro‐molecular synthesis . J. Pathol. , 142 , 67 – 77 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Sarraf , C. E. and Bowen , I. D.Proportions of mitotic and apoptotic cells in a range of untreated experimental tumours . Cell Tissue Kinet. , 21 , 45 – 119 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Hollowood , K. and Macartney , J. C.Reduced apoptotic cell death in follicular lymphoma . J. Pathol. , 163 , 337 – 342 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Gavrieli , Y. , Sherman , Y. and Ben‐Sasson , S. A.Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation . J. Cell Biol. , 119 , 493 – 501 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Shi , Y. , Szalay , M. G. , Paskar , L. , Boyer , M. , Singh , B. and Green , D. R.Activation‐induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation . J. Immunol. , 144 , 3326 – 3333 ( 1990. ). [PubMed] [Google Scholar]
  • 15. ) Tian , Q. , Streuli , M. , Saito , H. , Schlossman , S. F. and Anderson , P.A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells . Cell , 67 , 629 – 639 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Wijsman , J. H. , Jonker , R. R. , Keijzer , R. , Van De Velde , C. J. H. , Cornelisse , C. J. and Van Dierendonck , J. H.A new method to detect apoptosis in paraffin sections: in situ end‐labeling of fragmented DNA . J. Histochem. Cytochem. , 41 , 7 – 12 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Ansari , B. , Coates , P. J. , Greenstein , B. D. and Hall , P. A.In situ end‐labelling detects DNA strand breaks in apoptosis and other physiological and pathological states . J. Pathol. , 170 , 1 – 8 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Hsu , S.‐M. , Raine , L. and Fanger , H.Use of avidin‐biotin‐peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures . J. Histochem. Cytochem. , 29 , 577 – 580 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Japanese Research Society for Gastric Cancer . “The General Rules for the Gastric Cancer Study,” 12th Ed. ( 1993. ). Kanehara Shuppan; , Tokyo ( in Japanese ). [Google Scholar]
  • 20. ) Gorczyca , W. , Gong , J. and Darzynkiewicz , Z.Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynucleotidyl transferase and nick translation assays . Cancer Res. , 53 , 1945 – 1951 ( 1993. ). [PubMed] [Google Scholar]
  • 21. ) Yanagihara , K. and Tsumuraya , M.Transforming growth factor β1 induces apoptotic cell death in cultured human gastric carcinoma cells . Cancer Res. , 52 , 4042 – 4045 ( 1992. ). [PubMed] [Google Scholar]
  • 22. ) Ito , M. , Yasui , W. , Nakayama , H. , Yokozaki , H. , Ito , H. and Tahara , E.Reduced levels of transforming growth factor‐beta type I receptor in human gastric carcinomas . Jpn. J. Cancer Res. , 83 , 86 – 92 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. ) Hiraishi , K. , Suzuki , K. , Hakomori , S. and Adachi , M.Leyantigen expression is correlated with apoptosis (programmed cell death) . Glycobiology , 3 , 381 – 390 ( 1993. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES