Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1992 Apr;140(4):757–762.

Presence of Epstein-Barr virus in Hodgkin's disease is not exclusive to Reed-Sternberg cells.

G Khan 1, P J Coates 1, R K Gupta 1, H O Kangro 1, G Slavin 1
PMCID: PMC1886366  PMID: 1314022

Abstract

Thirty-three cases of Hodgkin's disease (HD) have been studied for the presence of Epstein-Barr virus (EBV) using a novel nonisotopic in situ hybridization procedure, based on the detection of Epstein-Barr encoded RNAs with oligonucleotide probes. An intense and morphologically distinct nuclear staining, sparing the nucleolus was seen in a total of 12 cases (36%). In six of these cases, the signal was located to the Hodgkin and Reed-Sternberg cells (HR-S); in the other six positive cases, the signal was observed only in the non-neoplastic small lymphocytes. These lymphocytes were few in number and immunocytochemistry results were consistent with a B-cell phenotype. The presence of EBV in those cases characterized by nuclear staining of small lymphocytes was confirmed by the polymerase chain reaction (PCR) analysis. The authors report the detection of EBV in small lymphocytes in HD by in situ hybridization and discuss the implications of these findings in relation to the proposed etiologic association between EBV and HD.

Full text

PDF
757

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. Coates P. J., Mak W. P., Slavin G., d'Ardenne A. J. Detection of single copies of Epstein-Barr virus in paraffin wax sections by non-radioactive in situ hybridisation. J Clin Pathol. 1991 Jun;44(6):487–491. doi: 10.1136/jcp.44.6.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coates P. J., Slavin G., D'Ardenne A. J. Persistence of Epstein-Barr virus in Reed-Sternberg cells throughout the course of Hodgkin's disease. J Pathol. 1991 Aug;164(4):291–297. doi: 10.1002/path.1711640404. [DOI] [PubMed] [Google Scholar]
  4. Eisinger M., Fox S. M., De Harven E., Biedler J. L., Sanders F. K. Virus-like agents from patients with Hodgkin's disease. Nature. 1971 Sep 10;233(5315):104–108. doi: 10.1038/233104a0. [DOI] [PubMed] [Google Scholar]
  5. Evans A. S., Gutensohn N. M. A population-based case-control study of EBV and other viral antibodies among persons with Hodgkin's disease and their siblings. Int J Cancer. 1984 Aug 15;34(2):149–157. doi: 10.1002/ijc.2910340203. [DOI] [PubMed] [Google Scholar]
  6. Gutensohn N., Cole P. Epidemiology of hodgkin's disease in the young. Int J Cancer. 1977 May 15;19(5):595–604. doi: 10.1002/ijc.2910190502. [DOI] [PubMed] [Google Scholar]
  7. Herbst H., Dallenbach F., Hummel M., Niedobitek G., Pileri S., Müller-Lantzsch N., Stein H. Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4766–4770. doi: 10.1073/pnas.88.11.4766. [DOI] [PMC free article] [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. Hirshaut Y., Reagan R. L., Perry S., De Vita V., Jr, Barile M. F. The search for a viral agent in Hodgkin's disease. Cancer. 1974 Oct;34(4):1080–1089. doi: 10.1002/1097-0142(197410)34:4<1080::aid-cncr2820340418>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  11. Howe J. G., Shu M. D. Isolation and characterization of the genes for two small RNAs of herpesvirus papio and their comparison with Epstein-Barr virus-encoded EBER RNAs. J Virol. 1988 Aug;62(8):2790–2798. doi: 10.1128/jvi.62.8.2790-2798.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Howe J. G., Steitz J. A. Localization of Epstein-Barr virus-encoded small RNAs by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9006–9010. doi: 10.1073/pnas.83.23.9006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hsu S. M., Raine L., Fanger H. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol. 1981 May;75(5):734–738. doi: 10.1093/ajcp/75.5.734. [DOI] [PubMed] [Google Scholar]
  14. Jackson D. P., Lewis F. A., Taylor G. R., Boylston A. W., Quirke P. Tissue extraction of DNA and RNA and analysis by the polymerase chain reaction. J Clin Pathol. 1990 Jun;43(6):499–504. doi: 10.1136/jcp.43.6.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Knecht H., Odermatt B. F., Bachmann E., Teixeira S., Sahli R., Hayoz D., Heitz P., Bachmann F. Frequent detection of Epstein-Barr virus DNA by the polymerase chain reaction in lymph node biopsies from patients with Hodgkin's disease without genomic evidence of B- or T-cell clonality. Blood. 1991 Aug 1;78(3):760–767. [PubMed] [Google Scholar]
  17. 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]
  18. Libetta C. M., Pringle J. H., Angel C. A., Craft A. W., Malcolm A. J., Lauder I. Demonstration of Epstein-Barr viral DNA in formalin-fixed, paraffin-embedded samples of Hodgkin's disease. J Pathol. 1990 Jul;161(3):255–260. doi: 10.1002/path.1711610313. [DOI] [PubMed] [Google Scholar]
  19. MACMAHON B. Epidemiological evidence of the nature of Hodgkin's disease. Cancer. 1957 Sep-Oct;10(5):1045–1054. doi: 10.1002/1097-0142(195709/10)10:5<1045::aid-cncr2820100527>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  20. MacMahon E. M., Glass J. D., Hayward S. D., Mann R. B., Becker P. S., Charache P., McArthur J. C., Ambinder R. F. Epstein-Barr virus in AIDS-related primary central nervous system lymphoma. Lancet. 1991 Oct 19;338(8773):969–973. doi: 10.1016/0140-6736(91)91837-k. [DOI] [PubMed] [Google Scholar]
  21. Masih A., Weisenburger D., Duggan M., Armitage J., Bashir R., Mitchell D., Wickert R., Purtilo D. T. Epstein-Barr viral genome in lymph nodes from patients with Hodgkin's disease may not be specific to Reed-Sternberg cells. Am J Pathol. 1991 Jul;139(1):37–43. [PMC free article] [PubMed] [Google Scholar]
  22. Miller G. The oncogenicity of Epstein-Barr virus. J Infect Dis. 1974 Aug;130(2):187–205. doi: 10.1093/infdis/130.2.187. [DOI] [PubMed] [Google Scholar]
  23. Mueller N. An epidemiologist's view of the new molecular biology findings in Hodgkin's disease. Ann Oncol. 1991 Feb;2 (Suppl 2):23–28. doi: 10.1007/978-1-4899-7305-4_3. [DOI] [PubMed] [Google Scholar]
  24. Mueller N. Epidemiologic studies assessing the role of the Epstein-Barr virus in Hodgkin's disease. Yale J Biol Med. 1987 Jul-Aug;60(4):321–332. [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Pallesen G., Hamilton-Dutoit S. J., Rowe M., Young L. S. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet. 1991 Feb 9;337(8737):320–322. doi: 10.1016/0140-6736(91)90943-j. [DOI] [PubMed] [Google Scholar]
  27. Pallesen G., Sandvej K., Hamilton-Dutoit S. J., Rowe M., Young L. S. Activation of Epstein-Barr virus replication in Hodgkin and Reed-Sternberg cells. Blood. 1991 Sep 1;78(5):1162–1165. [PubMed] [Google Scholar]
  28. Pope J. H., Horne M. K., Scott W. Transformation of foetal human keukocytes in vitro by filtrates of a human leukaemic cell line containing herpes-like virus. Int J Cancer. 1968 Nov 15;3(6):857–866. doi: 10.1002/ijc.2910030619. [DOI] [PubMed] [Google Scholar]
  29. Rocchi G., Felici A., Ragona G., Heinz A. Quantitative evaluation of Epstein-Barr-virus-infected mononuclear peripheral blood leukocytes in infectious mononucleosis. N Engl J Med. 1977 Jan 20;296(3):132–134. doi: 10.1056/NEJM197701202960302. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Stein H., Herbst H., Anagnostopoulos I., Niedobitek G., Dallenbach F., Kratzsch H. C. The nature of Hodgkin and Reed-Sternberg cells, their association with EBV, and their relationship to anaplastic large-cell lymphoma. Ann Oncol. 1991 Feb;2 (Suppl 2):33–38. doi: 10.1007/978-1-4899-7305-4_5. [DOI] [PubMed] [Google Scholar]
  32. Uhara H., Sato Y., Mukai K., Akao I., Matsuno Y., Furuya S., Hoshikawa T., Shimosato Y., Saida T. Detection of Epstein-Barr virus DNA in Reed-Sternberg cells of Hodgkin's disease using the polymerase chain reaction and in situ hybridization. Jpn J Cancer Res. 1990 Mar;81(3):272–278. doi: 10.1111/j.1349-7006.1990.tb02561.x. [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., 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]
  35. Wright C. F., Reid A. H., Tsai M. M., Ventre K. M., Murari P. J., Frizzera G., O'Leary T. J. Detection of Epstein-Barr virus sequences in Hodgkin's disease by the polymerase chain reaction. Am J Pathol. 1991 Aug;139(2):393–398. [PMC free article] [PubMed] [Google Scholar]
  36. Wu T. C., Mann R. B., Charache P., Hayward S. D., Staal S., Lambe B. C., Ambinder R. F. Detection of EBV gene expression in Reed-Sternberg cells of Hodgkin's disease. Int J Cancer. 1990 Nov 15;46(5):801–804. doi: 10.1002/ijc.2910460509. [DOI] [PubMed] [Google Scholar]

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

RESOURCES