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. 1993 Apr;142(4):1073–1079.

High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of HIV-associated Hodgkin's disease.

B G Herndier 1, H C Sanchez 1, K L Chang 1, Y Y Chen 1, L M Weiss 1
PMCID: PMC1886872  PMID: 8386441

Abstract

The Epstein-Barr virus (EBV) has been implicated in the pathogenesis of Hodgkin's disease, with an frequency of 15 to 50% in the immunocompetent host. We studied 12 formalin-fixed, paraffin-embedded cases of Hodgkin's disease occurring in human immunodeficiency virus-infected individuals to determine the frequency of EBV in Hodgkin's disease from this population. EBV DNA-RNA in situ hybridization was performed using a 30-base biotinylated anti-sense oligonucleotide complementary to the EBER1 gene of EBV. EBV RNA was found in the Reed-Sternberg cells and variants in 11 of 12 cases. Double-labeling studies confirmed the presence of EBV RNA in CD15-expressing Hodgkin's cells in all 11 cases, although rare B lymphocytes coexpressing EBV RNA and CD20 were also noted in these cases. The Hodgkin's cells in all 11 EBER-positive cases expressed latent membrane protein. The one case negative for EBV RNA showed the histology of nodular, lymphocyte predominance, a subtype thought to be distinct from other types of Hodgkin's disease.

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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. Audouin J., Diebold J., Pallesen G. Frequent expression of Epstein-Barr virus latent membrane protein-1 in tumour cells of Hodgkin's disease in HIV-positive patients. J Pathol. 1992 Aug;167(4):381–384. doi: 10.1002/path.1711670406. [DOI] [PubMed] [Google Scholar]
  3. Birx D. L., Redfield R. R., Tosato G. Defective regulation of Epstein-Barr virus infection in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related disorders. N Engl J Med. 1986 Apr 3;314(14):874–879. doi: 10.1056/NEJM198604033141403. [DOI] [PubMed] [Google Scholar]
  4. Brousset P., Chittal S., Schlaifer D., Icart J., Payen C., Rigal-Huguet F., Voigt J. J., Delsol G. Detection of Epstein-Barr virus messenger RNA in Reed-Sternberg cells of Hodgkin's disease by in situ hybridization with biotinylated probes on specially processed modified acetone methyl benzoate xylene (ModAMeX) sections. Blood. 1991 Apr 15;77(8):1781–1786. [PubMed] [Google Scholar]
  5. Glickman J. N., Howe J. G., Steitz J. A. Structural analyses of EBER1 and EBER2 ribonucleoprotein particles present in Epstein-Barr virus-infected cells. J Virol. 1988 Mar;62(3):902–911. doi: 10.1128/jvi.62.3.902-911.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Greenspan J. S., Greenspan D., Lennette E. T., Abrams D. I., Conant M. A., Petersen V., Freese U. K. Replication of Epstein-Barr virus within the epithelial cells of oral "hairy" leukoplakia, an AIDS-associated lesion. N Engl J Med. 1985 Dec 19;313(25):1564–1571. doi: 10.1056/NEJM198512193132502. [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., Steinbrecher E., Niedobitek G., Young L. S., Brooks L., Müller-Lantzsch N., Stein H. Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin's disease. Blood. 1992 Jul 15;80(2):484–491. [PubMed] [Google Scholar]
  10. Herndier B. G. Surgical pathology of HIV associated lymphoproliferations. Cancer Surv. 1991;10:135–149. [PubMed] [Google Scholar]
  11. Jarrett R. F., Gallagher A., Jones D. B., Alexander F. E., Krajewski A. S., Kelsey A., Adams J., Angus B., Gledhill S., Wright D. H. Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age. J Clin Pathol. 1991 Oct;44(10):844–848. doi: 10.1136/jcp.44.10.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Knowles D. M., Chamulak G., Subar M., Pelicci P. G., Dugan M., Burke J. S., Raphael B., Dalla-Favera R. Clinicopathologic, immunophenotypic, and molecular genetic analysis of AIDS-associated lymphoid neoplasia. Clinical and biologic implications. Pathol Annu. 1988;23(Pt 2):33–67. [PubMed] [Google Scholar]
  13. 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]
  14. McGrath M. S., Shiramizu B., Meeker T. C., Kaplan L. D., Herndier B. AIDS-associated polyclonal lymphoma: identification of a new HIV-associated disease process. J Acquir Immune Defic Syndr. 1991;4(4):408–415. [PubMed] [Google Scholar]
  15. Meeker T. C., Shiramizu B., Kaplan L., Herndier B., Sanchez H., Grimaldi J. C., Baumgartner J., Rachlin J., Feigal E., Rosenblum M. Evidence for molecular subtypes of HIV-associated lymphoma: division into peripheral monoclonal, polyclonal and central nervous system lymphoma. AIDS. 1991 Jun;5(6):669–674. [PubMed] [Google Scholar]
  16. Moore K. W., Vieira P., Fiorentino D. F., Trounstine M. L., Khan T. A., Mosmann T. R. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990 Jun 8;248(4960):1230–1234. doi: 10.1126/science.2161559. [DOI] [PubMed] [Google Scholar]
  17. Moran C. A., Tuur S., Angritt P., Reid A. H., O'Leary T. J. Epstein-Barr virus in Hodgkin's disease from patients with human immunodeficiency virus infection. Mod Pathol. 1992 Jan;5(1):85–88. [PubMed] [Google Scholar]
  18. 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]
  19. Pinkus G. S., Said J. W. Hodgkin's disease, lymphocyte predominance type, nodular--further evidence for a B cell derivation. L & H variants of Reed-Sternberg cells express L26, a pan B cell marker. Am J Pathol. 1988 Nov;133(2):211–217. [PMC free article] [PubMed] [Google Scholar]
  20. Regula D. P., Jr, Hoppe R. T., Weiss L. M. Nodular and diffuse types of lymphocyte predominance Hodgkin's disease. N Engl J Med. 1988 Jan 28;318(4):214–219. doi: 10.1056/NEJM198801283180404. [DOI] [PubMed] [Google Scholar]
  21. Rowe M., Evans H. S., Young L. S., Hennessy K., Kieff E., Rickinson A. B. Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in virus-transformed cells. J Gen Virol. 1987 Jun;68(Pt 6):1575–1586. doi: 10.1099/0022-1317-68-6-1575. [DOI] [PubMed] [Google Scholar]
  22. Samoszuk M., Ravel J. Frequent detection of Epstein-Barr viral deoxyribonucleic acid and absence of cytomegalovirus deoxyribonucleic acid in Hodgkin's disease and acquired immunodeficiency syndrome-related Hodgkin's disease. Lab Invest. 1991 Dec;65(6):631–636. [PubMed] [Google Scholar]
  23. Schoeppel S. L., Hoppe R. T., Dorfman R. F., Horning S. J., Collier A. C., Chew T. G., Weiss L. M. Hodgkin's disease in homosexual men with generalized lymphadenopathy. Ann Intern Med. 1985 Jan;102(1):68–70. doi: 10.7326/0003-4819-102-1-68. [DOI] [PubMed] [Google Scholar]
  24. Sheibani K., Tubbs R. R. Enzyme immunohistochemistry: technical aspects. Semin Diagn Pathol. 1984 Nov;1(4):235–250. [PubMed] [Google Scholar]
  25. Shibata D., Weiss L. M., Nathwani B. N., Brynes R. K., Levine A. M. Epstein-Barr virus in benign lymph node biopsies from individuals infected with the human immunodeficiency virus is associated with concurrent or subsequent development of non-Hodgkin's lymphoma. Blood. 1991 Apr 1;77(7):1527–1533. [PubMed] [Google Scholar]
  26. 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]
  27. Uccini S., Monardo F., Stoppacciaro A., Gradilone A., Aglianò A. M., Faggioni A., Manzari V., Vago L., Costanzi G., Ruco L. P. High frequency of Epstein-Barr virus genome detection in Hodgkin's disease of HIV-positive patients. Int J Cancer. 1990 Oct 15;46(4):581–585. doi: 10.1002/ijc.2910460405. [DOI] [PubMed] [Google Scholar]
  28. Weiss L. M., Chen Y. Y. Effects of different fixatives on detection of nucleic acids from paraffin-embedded tissues by in situ hybridization using oligonucleotide probes. J Histochem Cytochem. 1991 Sep;39(9):1237–1242. doi: 10.1177/39.9.1918942. [DOI] [PubMed] [Google Scholar]
  29. Weiss L. M., Chen Y. Y., Liu X. F., Shibata D. Epstein-Barr virus and Hodgkin's disease. A correlative in situ hybridization and polymerase chain reaction study. Am J Pathol. 1991 Dec;139(6):1259–1265. [PMC free article] [PubMed] [Google Scholar]
  30. Weiss L. M., Movahed L. A., Chen Y. Y., Shin S. S., Stroup R. M., Bui N., Estess P., Bindl J. M. Detection of immunoglobulin light-chain mRNA in lymphoid tissues using a practical in situ hybridization method. Am J Pathol. 1990 Oct;137(4):979–988. [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. 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]

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