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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Mar 21;82(8):1446–1452. doi: 10.1054/bjoc.1999.1073

Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms

S Munakata* 1, T Enomoto 2, M Tsujimoto 3, Y Otsuki 4, H Miwa 1, H Kanno 1, K Aozasa 1
PMCID: PMC2363379  PMID: 10780525

Abstract

SummaryExpression of apoptosis-related proteins, bcl-2, Bax, Fas and Fas ligand (L), in ovarian epithelial neoplasms together with its clinical relevance was examined by immunohistochemistry. They included 36 cases with adenoma, 33 with low potential malignancy (LPM) and 63 with carcinomas. bcl-2 expression was observed in 14 of 36 cases (39%) with adenoma, five of 33 (15%) with LPM (P< 0.05) and 12 of 63 (19%) with carcinoma (P< 0.05). Cases with bcl-2 expression showed more favourable prognosis than those without, but the difference was not statistically significant. There was no difference in frequency of Bax and Fas expression between each histologic category. Fas L expression was observed in one of 36 cases (3%) with adenoma, but in 12 of 33 (36%) with LPM (P< 0.001) and 42 of 63 (67%) with carcinoma (P< 0.0001). In carcinomas, cases expressing Fas L showed a less favourable prognosis than those without (P= 0.02). Density of CD8+ lymphocytes, possibly cytotoxic T-cells, was higher in serous carcinoma with negative Fas L expression than those with positive Fas L expression. These findings suggest that Fas L expressing carcinomas induce apoptosis in infiltrating CTL with Fas expression, and escape from immune surveillance. © 2000 Cancer Research Campaign

Keywords: Fas ligand, CD95 ligand, bcl-2, epithelial ovarian neoplasms, immunohistochemistry, prognosis

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Selected References

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  1. Bennett M. W., O'Connell J., O'Sullivan G. C., Brady C., Roche D., Collins J. K., Shanahan F. The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol. 1998 Jun 1;160(11):5669–5675. [PubMed] [Google Scholar]
  2. Brambilla E., Negoescu A., Gazzeri S., Lantuejoul S., Moro D., Brambilla C., Coll J. L. Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors. Am J Pathol. 1996 Dec;149(6):1941–1952. [PMC free article] [PubMed] [Google Scholar]
  3. Garzetti G. G., Ciavattini A., Goteri G., De Nictolis M., Stramazzotti D., Lucarini G., Biagini G. Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: index of proliferative activity with prognostic significance. Gynecol Oncol. 1995 Feb;56(2):169–174. doi: 10.1006/gyno.1995.1026. [DOI] [PubMed] [Google Scholar]
  4. Hahne M., Rimoldi D., Schröter M., Romero P., Schreier M., French L. E., Schneider P., Bornand T., Fontana A., Lienard D. Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science. 1996 Nov 22;274(5291):1363–1366. doi: 10.1126/science.274.5291.1363. [DOI] [PubMed] [Google Scholar]
  5. Hellquist H. B., Olejnicka B., Jadner M., Andersson T., Sederholm C. Fas receptor is expressed in human lung squamous cell carcinomas, whereas bcl-2 and apoptosis are not pronounced: a preliminary report. Br J Cancer. 1997;76(2):175–179. doi: 10.1038/bjc.1997.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Henriksen R., Funa K., Wilander E., Bäckström T., Ridderheim M., Oberg K. Expression and prognostic significance of platelet-derived growth factor and its receptors in epithelial ovarian neoplasms. Cancer Res. 1993 Oct 1;53(19):4550–4554. [PubMed] [Google Scholar]
  7. Henriksen R., Wilander E., Oberg K. Expression and prognostic significance of Bcl-2 in ovarian tumours. Br J Cancer. 1995 Nov;72(5):1324–1329. doi: 10.1038/bjc.1995.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
  9. Hoehner J. C., Gestblom C., Olsen L., Påhlman S. Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma. Br J Cancer. 1997;75(8):1185–1194. doi: 10.1038/bjc.1997.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hughes S. J., Nambu Y., Soldes O. S., Hamstra D., Rehemtulla A., Iannettoni M. D., Orringer M. B., Beer D. G. Fas/APO-1 (CD95) is not translocated to the cell membrane in esophageal adenocarcinoma. Cancer Res. 1997 Dec 15;57(24):5571–5578. [PubMed] [Google Scholar]
  11. Joensuu H., Pylkkänen L., Toikkanen S. Bcl-2 protein expression and long-term survival in breast cancer. Am J Pathol. 1994 Nov;145(5):1191–1198. [PMC free article] [PubMed] [Google Scholar]
  12. Katsube Y., Berg J. W., Silverberg S. G. Epidemiologic pathology of ovarian tumors: a histopathologic review of primary ovarian neoplasms diagnosed in the Denver Standard Metropolitan Statistical Area, 1 July-31 December 1969 and 1 July-31 December 1979. Int J Gynecol Pathol. 1982;1(1):3–16. doi: 10.1097/00004347-198201000-00003. [DOI] [PubMed] [Google Scholar]
  13. Koonings P. P., Campbell K., Mishell D. R., Jr, Grimes D. A. Relative frequency of primary ovarian neoplasms: a 10-year review. Obstet Gynecol. 1989 Dec;74(6):921–926. [PubMed] [Google Scholar]
  14. Landowski T. H., Qu N., Buyuksal I., Painter J. S., Dalton W. S. Mutations in the Fas antigen in patients with multiple myeloma. Blood. 1997 Dec 1;90(11):4266–4270. [PubMed] [Google Scholar]
  15. McDonnell T. J., Deane N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989 Apr 7;57(1):79–88. doi: 10.1016/0092-8674(89)90174-8. [DOI] [PubMed] [Google Scholar]
  16. Müllauer L., Mosberger I., Chott A. Fas ligand expression in nodal non-Hodgkin's lymphoma. Mod Pathol. 1998 Apr;11(4):369–375. [PubMed] [Google Scholar]
  17. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  18. Niehans G. A., Brunner T., Frizelle S. P., Liston J. C., Salerno C. T., Knapp D. J., Green D. R., Kratzke R. A. Human lung carcinomas express Fas ligand. Cancer Res. 1997 Mar 15;57(6):1007–1012. [PubMed] [Google Scholar]
  19. Oltvai Z. N., Milliman C. L., Korsmeyer S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609–619. doi: 10.1016/0092-8674(93)90509-o. [DOI] [PubMed] [Google Scholar]
  20. Omura G. A., Brady M. F., Homesley H. D., Yordan E., Major F. J., Buchsbaum H. J., Park R. C. Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience. J Clin Oncol. 1991 Jul;9(7):1138–1150. doi: 10.1200/JCO.1991.9.7.1138. [DOI] [PubMed] [Google Scholar]
  21. Owen-Schaub L. B., Radinsky R., Kruzel E., Berry K., Yonehara S. Anti-Fas on nonhematopoietic tumors: levels of Fas/APO-1 and bcl-2 are not predictive of biological responsiveness. Cancer Res. 1994 Mar 15;54(6):1580–1586. [PubMed] [Google Scholar]
  22. Pezzella F., Turley H., Kuzu I., Tungekar M. F., Dunnill M. S., Pierce C. B., Harris A., Gatter K. C., Mason D. Y. bcl-2 protein in non-small-cell lung carcinoma. N Engl J Med. 1993 Sep 2;329(10):690–694. doi: 10.1056/NEJM199309023291003. [DOI] [PubMed] [Google Scholar]
  23. Rodenburg C. J., Cornelisse C. J., Heintz P. A., Hermans J., Fleuren G. J. Tumor ploidy as a major prognostic factor in advanced ovarian cancer. Cancer. 1987 Jan 15;59(2):317–323. doi: 10.1002/1097-0142(19870115)59:2<317::aid-cncr2820590225>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  24. Shima Y., Nishimoto N., Ogata A., Fujii Y., Yoshizaki K., Kishimoto T. Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis. Blood. 1995 Feb 1;85(3):757–764. [PubMed] [Google Scholar]
  25. Shiraki K., Tsuji N., Shioda T., Isselbacher K. J., Takahashi H. Expression of Fas ligand in liver metastases of human colonic adenocarcinomas. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6420–6425. doi: 10.1073/pnas.94.12.6420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J., Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. doi: 10.1126/science.2470152. [DOI] [PubMed] [Google Scholar]
  27. Strand S., Hofmann W. J., Hug H., Müller M., Otto G., Strand D., Mariani S. M., Stremmel W., Krammer P. H., Galle P. R. Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion? Nat Med. 1996 Dec;2(12):1361–1366. doi: 10.1038/nm1296-1361. [DOI] [PubMed] [Google Scholar]
  28. Takahashi T., Tanaka M., Inazawa J., Abe T., Suda T., Nagata S. Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol. 1994 Oct;6(10):1567–1574. doi: 10.1093/intimm/6.10.1567. [DOI] [PubMed] [Google Scholar]
  29. Tanaka M., Suda T., Haze K., Nakamura N., Sato K., Kimura F., Motoyoshi K., Mizuki M., Tagawa S., Ohga S. Fas ligand in human serum. Nat Med. 1996 Mar;2(3):317–322. doi: 10.1038/nm0396-317. [DOI] [PubMed] [Google Scholar]
  30. Ungefroren H., Voss M., Jansen M., Roeder C., Henne-Bruns D., Kremer B., Kalthoff H. Human pancreatic adenocarcinomas express Fas and Fas ligand yet are resistant to Fas-mediated apoptosis. Cancer Res. 1998 Apr 15;58(8):1741–1749. [PubMed] [Google Scholar]
  31. Wakahara Y., Nawa A., Okamoto T., Hayakawa A., Kikkawa F., Suganama N., Wakahara F., Tomoda Y. Combination effect of anti-Fas antibody and chemotherapeutic drugs in ovarian cancer cells in vitro. Oncology. 1997 Jan-Feb;54(1):48–54. doi: 10.1159/000227661. [DOI] [PubMed] [Google Scholar]
  32. Wehrli B. M., Krajewski S., Gascoyne R. D., Reed J. C., Gilks C. B. Immunohistochemical analysis of bcl-2, bax, mcl-1, and bcl-X expression in ovarian surface epithelial tumors. Int J Gynecol Pathol. 1998 Jul;17(3):255–260. doi: 10.1097/00004347-199807000-00010. [DOI] [PubMed] [Google Scholar]

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