Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Mar;148(3):847–853.

Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease.

P L Nguyen 1, N L Harris 1, J Ritz 1, M J Robertson 1
PMCID: PMC1861710  PMID: 8774139

Abstract

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerve growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 expression is upregulated on activated T and B lymphocytes and natural killer cells, where binding of the antigen by anti-Fas and anti-APO-1 antibodies has been shown to induce apoptosis. This CD95-mediated apoptosis is at least partially inhibited by expression of the Bcl-2 protooncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regulation of lymphoid neoplasms, we studied by immunohistochemistry the expression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 cases of Hodgkin's disease. In all, 29 B and 2 T cell lymphomas, and 9 cases of Hodgkin's disease expressed CD95. Compared with diffuse large B-cell and Burkitt-like lymphomas, lowgrade B-cell lymphomas more frequently expressed CD95 (52% versus 26%; P < .005). None of the B-cell small lymphocytic lymphomas or mantle cell lymphomas expressed CD95, whereas the majority of follicle center lymphomas, extranodal marginal zone B-cell lymphomas, and immunocytomas were CD95+. Of the 29 CD95+ B-cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, compared with 87% of the low-grade group (P < .04). Two of three peripheral T-cell lymphomas--including one anaplastic large cell lymphoma--expressed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's disease. The infrequent expression of CD95 in high-grade B-cell lymphomas suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediated apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the apoptosis signal delivered by CD95.

Full text

PDF
847

Images in this article

849Figure 1
on p.849
850Figure 2
on p.850

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Camerini D., Walz G., Loenen W. A., Borst J., Seed B. The T cell activation antigen CD27 is a member of the nerve growth factor/tumor necrosis factor receptor gene family. J Immunol. 1991 Nov 1;147(9):3165–3169. [PubMed] [Google Scholar]
  2. Debatin K. M., Goldmann C. K., Bamford R., Waldmann T. A., Krammer P. H. Monoclonal-antibody-mediated apoptosis in adult T-cell leukaemia. Lancet. 1990 Mar 3;335(8688):497–500. doi: 10.1016/0140-6736(90)90735-n. [DOI] [PubMed] [Google Scholar]
  3. Dürkop H., Latza U., Hummel M., Eitelbach F., Seed B., Stein H. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. Cell. 1992 Feb 7;68(3):421–427. doi: 10.1016/0092-8674(92)90180-k. [DOI] [PubMed] [Google Scholar]
  4. Falk M. H., Trauth B. C., Debatin K. M., Klas C., Gregory C. D., Rickinson A. B., Calender A., Lenoir G. M., Ellwart J. W., Krammer P. H. Expression of the APO-1 antigen in Burkitt lymphoma cell lines correlates with a shift towards a lymphoblastoid phenotype. Blood. 1992 Jun 15;79(12):3300–3306. [PubMed] [Google Scholar]
  5. Ferry J. A., Linggood R. M., Convery K. M., Efird J. T., Eliseo R., Harris N. L. Hodgkin disease, nodular sclerosis type. Implications of histologic subclassification. Cancer. 1993 Jan 15;71(2):457–463. doi: 10.1002/1097-0142(19930115)71:2<457::aid-cncr2820710229>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  6. Gruss H. J., Dower S. K. Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. Blood. 1995 Jun 15;85(12):3378–3404. [PubMed] [Google Scholar]
  7. Harris N. L., Data R. E. The distribution of neoplastic and normal B-lymphoid cells in nodular lymphomas: use of an immunoperoxidase technique on frozen sections. Hum Pathol. 1982 Jul;13(7):610–617. doi: 10.1016/s0046-8177(82)80002-6. [DOI] [PubMed] [Google Scholar]
  8. Itoh N., Tsujimoto Y., Nagata S. Effect of bcl-2 on Fas antigen-mediated cell death. J Immunol. 1993 Jul 15;151(2):621–627. [PubMed] [Google Scholar]
  9. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  10. Iwai K., Miyawaki T., Takizawa T., Konno A., Ohta K., Yachie A., Seki H., Taniguchi N. Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils. Blood. 1994 Aug 15;84(4):1201–1208. [PubMed] [Google Scholar]
  11. Johnson D., Lanahan A., Buck C. R., Sehgal A., Morgan C., Mercer E., Bothwell M., Chao M. Expression and structure of the human NGF receptor. Cell. 1986 Nov 21;47(4):545–554. doi: 10.1016/0092-8674(86)90619-7. [DOI] [PubMed] [Google Scholar]
  12. Klas C., Debatin K. M., Jonker R. R., Krammer P. H. Activation interferes with the APO-1 pathway in mature human T cells. Int Immunol. 1993 Jun;5(6):625–630. doi: 10.1093/intimm/5.6.625. [DOI] [PubMed] [Google Scholar]
  13. Kondo E., Yoshino T., Yamadori I., Matsuo Y., Kawasaki N., Minowada J., Akagi T. Expression of Bcl-2 protein and Fas antigen in non-Hodgkin's lymphomas. Am J Pathol. 1994 Aug;145(2):330–337. [PMC free article] [PubMed] [Google Scholar]
  14. Leithäuser F., Dhein J., Mechtersheimer G., Koretz K., Brüderlein S., Henne C., Schmidt A., Debatin K. M., Krammer P. H., Möller P. Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab Invest. 1993 Oct;69(4):415–429. [PubMed] [Google Scholar]
  15. Lichter P., Walczak H., Weitz S., Behrmann I., Krammer P. H. The human APO-1 (APT) antigen maps to 10q23, a region that is syntenic with mouse chromosome 19. Genomics. 1992 Sep;14(1):179–180. doi: 10.1016/s0888-7543(05)80302-7. [DOI] [PubMed] [Google Scholar]
  16. Loetscher H., Pan Y. C., Lahm H. W., Gentz R., Brockhaus M., Tabuchi H., Lesslauer W. Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell. 1990 Apr 20;61(2):351–359. doi: 10.1016/0092-8674(90)90815-v. [DOI] [PubMed] [Google Scholar]
  17. Mapara M. Y., Bargou R., Zugck C., Döhner H., Ustaoglu F., Jonker R. R., Krammer P. H., Dörken B. APO-1 mediated apoptosis or proliferation in human chronic B lymphocytic leukemia: correlation with bcl-2 oncogene expression. Eur J Immunol. 1993 Mar;23(3):702–708. doi: 10.1002/eji.1830230320. [DOI] [PubMed] [Google Scholar]
  18. Miyawaki T., Uehara T., Nibu R., Tsuji T., Yachie A., Yonehara S., Taniguchi N. Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. J Immunol. 1992 Dec 1;149(11):3753–3758. [PubMed] [Google Scholar]
  19. Munker R., Lübbert M., Yonehara S., Tuchnitz A., Mertelsmann R., Wilmanns W. Expression of the Fas antigen on primary human leukemia cells. Ann Hematol. 1995 Jan;70(1):15–17. doi: 10.1007/BF01715376. [DOI] [PubMed] [Google Scholar]
  20. Möller P., Henne C., Leithäuser F., Eichelmann A., Schmidt A., Brüderlein S., Dhein J., Krammer P. H. Coregulation of the APO-1 antigen with intercellular adhesion molecule-1 (CD54) in tonsillar B cells and coordinate expression in follicular center B cells and in follicle center and mediastinal B-cell lymphomas. Blood. 1993 Apr 15;81(8):2067–2075. [PubMed] [Google Scholar]
  21. Möller P., Koretz K., Leithäuser F., Brüderlein S., Henne C., Quentmeier A., Krammer P. H. Expression of APO-1 (CD95), a member of the NGF/TNF receptor superfamily, in normal and neoplastic colon epithelium. Int J Cancer. 1994 May 1;57(3):371–377. doi: 10.1002/ijc.2910570314. [DOI] [PubMed] [Google Scholar]
  22. Oehm A., Behrmann I., Falk W., Pawlita M., Maier G., Klas C., Li-Weber M., Richards S., Dhein J., Trauth B. C. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem. 1992 May 25;267(15):10709–10715. [PubMed] [Google Scholar]
  23. Owen-Schaub L. B., Yonehara S., Crump W. L., 3rd, Grimm E. A. DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement. Cell Immunol. 1992 Mar;140(1):197–205. doi: 10.1016/0008-8749(92)90187-t. [DOI] [PubMed] [Google Scholar]
  24. Robertson M. J., Manley T. J., Pichert G., Cameron C., Cochran K. J., Levine H., Ritz J. Functional consequences of APO-1/Fas (CD95) antigen expression by normal and neoplastic hematopoietic cells. Leuk Lymphoma. 1995 Mar;17(1-2):51–61. doi: 10.3109/10428199509051703. [DOI] [PubMed] [Google Scholar]
  25. Schall T. J., Lewis M., Koller K. J., Lee A., Rice G. C., Wong G. H., Gatanaga T., Granger G. A., Lentz R., Raab H. Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell. 1990 Apr 20;61(2):361–370. doi: 10.1016/0092-8674(90)90816-w. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Stamenkovic I., Clark E. A., Seed B. A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J. 1989 May;8(5):1403–1410. doi: 10.1002/j.1460-2075.1989.tb03521.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Suda T., Takahashi T., Golstein P., Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993 Dec 17;75(6):1169–1178. doi: 10.1016/0092-8674(93)90326-l. [DOI] [PubMed] [Google Scholar]
  29. Trauth B. C., Klas C., Peters A. M., Matzku S., Möller P., Falk W., Debatin K. M., Krammer P. H. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 1989 Jul 21;245(4915):301–305. doi: 10.1126/science.2787530. [DOI] [PubMed] [Google Scholar]
  30. Yonehara S., Ishii A., Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med. 1989 May 1;169(5):1747–1756. doi: 10.1084/jem.169.5.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yoshino T., Kondo E., Cao L., Takahashi K., Hayashi K., Nomura S., Akagi T. Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral lymph nodes and activated peripheral blood T and B lymphocytes. Blood. 1994 Apr 1;83(7):1856–1861. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES