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Prognostic Significance of Fas and Fas Ligand System-Associated Apoptosis in Gastric Cancer

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Abstract

Background: Previous studies indicate that gastric carcinomas express Fas ligand and downregulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated.

Methods: Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method.

Results: The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD81 cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients’ age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD81 cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors.

Conclusions: Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD81 cells.

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References

  1. White E. Life, death, and the pursuit of apoptosis. Genes Dev 1996;10:1–15.

    CAS  PubMed  Google Scholar 

  2. Ikeguchi M., Cai J., Yamane N., Maeta M., Kaibara N. Clinical significance of spontaneous apoptosis in advanced gastric adenocarcinoma. Cancer 1999;85:2329–2335.

    CAS  PubMed  Google Scholar 

  3. Ohtani M., Isozaki H., Fujii K, et al. Impact of the expression of cyclin-dependent kinase inhibitor p27Kip1 and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma. Cancer 1999;85:1711–1718.

    CAS  PubMed  Google Scholar 

  4. Xie X., Clausen OPF., Angelis PD., Boysen M. The prognostic value of spontaneous apoptosis, Bax, Bcl-2, and p53 in oral squamous cell carcinoma of the tongue. Cancer 1999;86:913–920.

    CAS  PubMed  Google Scholar 

  5. Sinicrope FA., Hart J., Hsu HA., Lemoine M., Michelassi F., Stephens LC. Apoptotic and mitotic indices predict survival rates in lymph node-negative colon carcinoma. Clin Cancer Res 1999;5:1793–1804.

    CAS  PubMed  Google Scholar 

  6. Matturri L., Colombo B., Lavezzi AM. Evidence for apoptosis in non-small cell lung carcinoma. Relationship with cell kinetics and prognosis. Anal Quant Cytol Histol 1999;21:240–244.

    CAS  PubMed  Google Scholar 

  7. Tnaka K., Iwamoto S., Gon G., Nohara T., Iwamoto M., Tanigawa N. Expression of survivin and its relationship to loss apoptosis in breast carcinoma. Clin Cancer Res 2000;6:127–134.

    Google Scholar 

  8. Nagata S. Apoptosis by death factor. Cell 1997;88:355–365.

    Article  CAS  PubMed  Google Scholar 

  9. Hundahl SA., Phillips JL., Menck HR. The national Cancer data base report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy. Cancer 2000;88:921–932.

    CAS  PubMed  Google Scholar 

  10. Strand S., Hofmann WJ., Hug H, et al. Lymphocyte apoptosis induced by CD95(APO-1/Fas)ligand-expressing tumor cells–A mechanism of immune evasion? Nature Med 1996;2:1361–1316.

    CAS  PubMed  Google Scholar 

  11. Bennett MW., O’Connell J., O’Sullivan GC, et al. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer. Gut 1999;44:156–162.

    Article  CAS  PubMed  Google Scholar 

  12. Koomagi R., Volm M. Expression of Fas (CD95/APO-1) and Fas ligand in lung cancer, its prognostic and predictive relevance. Int J Cancer 1999;84:239–243.

    CAS  PubMed  Google Scholar 

  13. Nagao M., Nakajima Y., Hisanaga M, et al. The alteration of Fas receptor and ligand system in hepatocellular carcinomas: How do hepatoma cells escape from the host immune surveillance in vivo? Hepatology 1999;30:413–21.

    Article  CAS  PubMed  Google Scholar 

  14. Shibakita M., Tachibana M., Dahr DK, et al. Prognostic significance of Fas and Fas ligand expression in human esophageal cancer. Clin Cancer Res 1999;5:2464–2469.

    CAS  PubMed  Google Scholar 

  15. Rosenberg SA. The immunotherapy of solid cancers based on cloning the genes encoding tumor-rejection antigens. Annu Rev Med 1996;47:481–491.

    CAS  PubMed  Google Scholar 

  16. Nagata S., Golstein P. The Fas death factor. Science 1995;267:1149–1156.

    Google Scholar 

  17. Naito Y., Saito K., Shiiba K., Ohuchi A., Saigenji K., Nagura H., Ohtani H. CD81 T cells infiltrated within cancer nests as a prognostic factor in human colorectal cancer. Cancer Res 1998;58:3491–3494.

    CAS  PubMed  Google Scholar 

  18. Ishigami S., Natsugoe S., Tokuda K, et al. Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer 2000;88:577–583.

    Article  CAS  PubMed  Google Scholar 

  19. International Union Against Cancer. TNM Classification of Malignant Tumors. 5th edition. New York: Willy-Liss, 1997.

    Google Scholar 

  20. Gavrieli Y., Sherman Y., Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992;119:493–501.

    Article  CAS  PubMed  Google Scholar 

  21. Ansari B., Cortes PJ., Greenstein BD., Hall PA. In situ end-labeling detects DNA strand breaks in apoptosis and other physiological and pathological states. J Pathol 1993;170:1–8.

    CAS  PubMed  Google Scholar 

  22. Kaplan EL., Meier P. Nonparametric estimation for incomplete observation. J Am Stat Assoc 1958;53:457–481.

    Google Scholar 

  23. Cox DR. Regression models and life tables. J R Stat Soc Ser B 1972;34:187–220.

    Google Scholar 

  24. Lee SH., Kim SY., Lee JY, et al. Detection of soluble Fas mRNA using in situ reverse transcription-polymerase chain reaction. Lab Invest 1998;78:453–459.

    CAS  PubMed  Google Scholar 

  25. Bellgrau D., Gold D., Selawry H., More J., Franzusoff A., Duke RC. A role for CD95 ligand in preventing graft rejection. Nature 1995;377:630–632.

    CAS  PubMed  Google Scholar 

  26. Griffith TS., Brunner T., Fletcher SM., Green DR., Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995;270:1189–1192.

    CAS  PubMed  Google Scholar 

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Correspondence to Satoshi Ohno MD.

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Ohno, S., Tachibana, M., Shibakita, M. et al. Prognostic Significance of Fas and Fas Ligand System-Associated Apoptosis in Gastric Cancer. Ann Surg Oncol 7, 750–757 (2000). https://doi.org/10.1007/s10434-000-0750-1

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  • DOI: https://doi.org/10.1007/s10434-000-0750-1

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