Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1991 Jul;139(1):37–43.

Epstein-Barr viral genome in lymph nodes from patients with Hodgkin's disease may not be specific to Reed-Sternberg cells.

A Masih 1, D Weisenburger 1, M Duggan 1, J Armitage 1, R Bashir 1, D Mitchell 1, R Wickert 1, D T Purtilo 1
PMCID: PMC1886130  PMID: 1649556

Abstract

A possible etiologic role for Epstein-Barr virus (EBV) in Hodgkin's disease (HD) was investigated by probing for EBV genome in 52 biopsy specimens involved with HD and 43 hyperplastic lymph node specimens. Using dot-blot hybridization (Bam HIW probe), Southern blot hybridization (Xho I probe), and polymerase chain reaction analyses, 27%, 27%, and 58% of the nodes with HD were positive for EBV genome, respectively, as compared to 16%, 14%, and 43% in the hyperplastic lymph nodes. Clonal and nonclonal episomal EBV and linear replicating EBV genome were present in both conditions. Immunoglobulin heavy chain gene rearrangements were found in two clonal and two nonclonal EBV-positive HD cases, but not in the lymphoid hyperplasia cases. These findings and other recent reports showing EBV genome in benign lymphoid cells by in situ hybridization in Hodgkin's disease suggest that the characteristics of EBV infection in HD could be explained by the reactive cellular milieu, especially in the setting of defective immunity. The identification of EBV genome in Reed-Sternberg cells may, therefore, be a nonspecific phenomenon.

Full text

PDF
40

Images in this article

Selected References

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

  1. Anagnostopoulos I., Herbst H., Niedobitek G., Stein H. Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. Blood. 1989 Aug 1;74(2):810–816. [PubMed] [Google Scholar]
  2. Bashir R., Hochberg F., Singer R. H. Detection of Epstein-Barr virus by in situ hybridization. Progress toward development of a nonisotopic diagnostic test. Am J Pathol. 1989 Dec;135(6):1035–1044. [PMC free article] [PubMed] [Google Scholar]
  3. Boiocchi M., Carbone A., De Re V., Dolcetti R. Is the Epstein-Barr virus involved in Hodgkin's disease? Tumori. 1989 Aug 31;75(4):345–350. doi: 10.1177/030089168907500409. [DOI] [PubMed] [Google Scholar]
  4. Drexler H. G., Amlot P. L., Minowada J. Hodgkin's disease-derived cell lines--conflicting clues for the origin of Hodgkin's disease? Leukemia. 1987 Sep;1(9):629–637. [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  6. Griesser H., Feller A., Lennert K., Minden M., Mak T. W. Rearrangement of the beta chain of the T cell antigen receptor and immunoglobulin genes in lymphoproliferative disorders. J Clin Invest. 1986 Nov;78(5):1179–1184. doi: 10.1172/JCI112700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guarner J., del Rio C., Hendrix L., Unger E. R. Composite Hodgkin's and non-Hodgkin's lymphoma in a patient with acquired immune deficiency syndrome. In-situ demonstration of Epstein-Barr virus. Cancer. 1990 Aug 15;66(4):796–800. doi: 10.1002/1097-0142(19900815)66:4<796::aid-cncr2820660433>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  8. Herbst H., Niedobitek G., Kneba M., Hummel M., Finn T., Anagnostopoulos I., Bergholz M., Krieger G., Stein H. High incidence of Epstein-Barr virus genomes in Hodgkin's disease. Am J Pathol. 1990 Jul;137(1):13–18. [PMC free article] [PubMed] [Google Scholar]
  9. Herbst H., Tippelmann G., Anagnostopoulos I., Gerdes J., Schwarting R., Boehm T., Pileri S., Jones D. B., Stein H. Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma: dissociation between phenotype and genotype. Leuk Res. 1989;13(2):103–116. doi: 10.1016/0145-2126(89)90134-3. [DOI] [PubMed] [Google Scholar]
  10. Hesse J., Andersen E., Levine P. H., Ebbesen P., Halberg P., Reisher J. I. Antibody to Epstein-Barr virus and cellular immunity in Hodgkin's disease and chronic lymphatic leukemia. Int J Cancer. 1973 Jan 15;11(1):237–243. doi: 10.1002/ijc.2910110128. [DOI] [PubMed] [Google Scholar]
  11. Hsu S. M., Yang K., Jaffe E. S. Phenotypic expression of Hodgkin's and Reed-Sternberg cells in Hodgkin's disease. Am J Pathol. 1985 Feb;118(2):209–217. [PMC free article] [PubMed] [Google Scholar]
  12. Johansson B., Klein G., Henle W., Henle G. Epstein-Barr virus (EBV)-associated antibody patterns in malignant lymphoma and leukemia. I. Hodgkin's disease. Int J Cancer. 1970 Nov 15;6(3):450–462. doi: 10.1002/ijc.2910060316. [DOI] [PubMed] [Google Scholar]
  13. Kadin M. E., Stites D. P., Levy R., Warnke R. Exogenous immunoglobulin and the macrophage origin of Reed-Sternberg cells in Hodgkin's disease. N Engl J Med. 1978 Nov 30;299(22):1208–1214. doi: 10.1056/NEJM197811302992203. [DOI] [PubMed] [Google Scholar]
  14. Katz B. Z., Raab-Traub N., Miller G. Latent and replicating forms of Epstein-Barr virus DNA in lymphomas and lymphoproliferative diseases. J Infect Dis. 1989 Oct;160(4):589–598. doi: 10.1093/infdis/160.4.589. [DOI] [PubMed] [Google Scholar]
  15. Knowles D. M., 2nd, Neri A., Pelicci P. G., Burke J. S., Wu A., Winberg C. D., Sheibani K., Dalla-Favera R. Immunoglobulin and T-cell receptor beta-chain gene rearrangement analysis of Hodgkin's disease: implications for lineage determination and differential diagnosis. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7942–7946. doi: 10.1073/pnas.83.20.7942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Levine P. H., Ablashi D. V., Berard C. W., Carbone P. P., Waggoner D. E., Malan L. Elevated antibody titers to Epstein-Barr virus in Hodgkin's disease. Cancer. 1971 Feb;27(2):416–421. doi: 10.1002/1097-0142(197102)27:2<416::aid-cncr2820270227>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  17. Lindahl T., Klein G., Reedman B. M., Johansson B., Singh S. Relationship between Epstein-Barr virus (EBV) DNA and the EBV-determined nuclear antigen (EBNA) in Burkitt lymphoma biopsies and other lymphoproliferative malignancies. Int J Cancer. 1974 Jun 15;13(6):764–772. doi: 10.1002/ijc.2910130605. [DOI] [PubMed] [Google Scholar]
  18. Locker J., Nalesnik M. Molecular genetic analysis of lymphoid tumors arising after organ transplantation. Am J Pathol. 1989 Dec;135(6):977–987. [PMC free article] [PubMed] [Google Scholar]
  19. Lukes R. J., Butler J. J. The pathology and nomenclature of Hodgkin's disease. Cancer Res. 1966 Jun;26(6):1063–1083. [PubMed] [Google Scholar]
  20. Mueller N., Evans A., Harris N. L., Comstock G. W., Jellum E., Magnus K., Orentreich N., Polk B. F., Vogelman J. Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med. 1989 Mar 16;320(11):689–695. doi: 10.1056/NEJM198903163201103. [DOI] [PubMed] [Google Scholar]
  21. Penn I. Cancers complicating organ transplantation. N Engl J Med. 1990 Dec 20;323(25):1767–1769. doi: 10.1056/NEJM199012203232510. [DOI] [PubMed] [Google Scholar]
  22. Purtilo D. T., Falk K., Pirruccello S. J., Nakamine H., Kleveland K., Davis J. R., Okano M., Taguchi Y., Sanger W. G., Beisel K. W. SCID mouse model of Epstein-Barr virus-induced lymphomagenesis of immunodeficient humans. Int J Cancer. 1991 Feb 20;47(4):510–517. doi: 10.1002/ijc.2910470407. [DOI] [PubMed] [Google Scholar]
  23. Raab-Traub N., Flynn K. The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell. 1986 Dec 26;47(6):883–889. doi: 10.1016/0092-8674(86)90803-2. [DOI] [PubMed] [Google Scholar]
  24. Randhawa P. S., Jaffe R., Demetris A. J., Nalesnik M., Starzl T. E., Chen Y. Y., Weiss L. M. The systemic distribution of Epstein-Barr virus genomes in fatal post-transplantation lymphoproliferative disorders. An in situ hybridization study. Am J Pathol. 1991 Apr;138(4):1027–1033. [PMC free article] [PubMed] [Google Scholar]
  25. Roth M. S., Schnitzer B., Bingham E. L., Harnden C. E., Hyder D. M., Ginsburg D. Rearrangement of immunoglobulin and T-cell receptor genes in Hodgkin's disease. Am J Pathol. 1988 May;131(2):331–338. [PMC free article] [PubMed] [Google Scholar]
  26. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  27. Staal S. P., Ambinder R., Beschorner W. E., Hayward G. S., Mann R. A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin's disease. Am J Clin Pathol. 1989 Jan;91(1):1–5. doi: 10.1093/ajcp/91.1.1. [DOI] [PubMed] [Google Scholar]
  28. Stevenson M., Volsky B., Hedenskog M., Volsky D. J. Immortalization of human T lymphocytes after transfection of Epstein-Barr virus DNA. Science. 1986 Aug 29;233(4767):980–984. doi: 10.1126/science.3016899. [DOI] [PubMed] [Google Scholar]
  29. Su I. J., Lin K. H., Chen C. J., Tien H. F., Hsieh H. C., Lin D. T., Chen J. Y. Epstein-Barr virus-associated peripheral T-cell lymphoma of activated CD8 phenotype. Cancer. 1990 Dec 15;66(12):2557–2562. doi: 10.1002/1097-0142(19901215)66:12<2557::aid-cncr2820661218>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  30. Sundeen J., Lipford E., Uppenkamp M., Sussman E., Wahl L., Raffeld M., Cossman J. Rearranged antigen receptor genes in Hodgkin's disease. Blood. 1987 Jul;70(1):96–103. [PubMed] [Google Scholar]
  31. Tindle B. H., Parker J. W., Lukes R. J. "Reed-Sternberg cells" in infectious mononucleosis? Am J Clin Pathol. 1972 Dec;58(6):607–617. doi: 10.1093/ajcp/58.6.607. [DOI] [PubMed] [Google Scholar]
  32. Tosato G., Steinberg A. D., Yarchoan R., Heilman C. A., Pike S. E., De Seau V., Blaese R. M. Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis. J Clin Invest. 1984 Jun;73(6):1789–1795. doi: 10.1172/JCI111388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weiss L. M., Movahed L. A., Warnke R. A., Sklar J. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease. N Engl J Med. 1989 Feb 23;320(8):502–506. doi: 10.1056/NEJM198902233200806. [DOI] [PubMed] [Google Scholar]
  34. Weiss L. M., Strickler J. G., Hu E., Warnke R. A., Sklar J. Immunoglobulin gene rearrangements in Hodgkin's disease. Hum Pathol. 1986 Oct;17(10):1009–1014. doi: 10.1016/s0046-8177(86)80084-3. [DOI] [PubMed] [Google Scholar]
  35. Weiss L. M., Strickler J. G., Warnke R. A., Purtilo D. T., Sklar J. Epstein-Barr viral DNA in tissues of Hodgkin's disease. Am J Pathol. 1987 Oct;129(1):86–91. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES