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. 1995 Nov;147(5):1408–1415.

Detection of Epstein-Barr virus in multiple sites involved by Hodgkin's disease.

M A Vasef 1, O W Kamel 1, Y Y Chen 1, L J Medeiros 1, L M Weiss 1
PMCID: PMC1869524  PMID: 7485403

Abstract

Tissues obtained from 14 patients with multiple anatomic sites involved by Hodgkin's disease were studied for Epstein-Barr virus (EBV) using in situ hybridization for EBV-encoded RNA (EBER) 1 and immunohistochemical methods for EBV latent membrane protein (LMP) expression. Each patient in this study had two to five separately involved anatomic sites, and all biopsy sites, a total of 43 specimens, were analyzed for EBV. EBV was detected in 6 of 14 (42.8%) patients with Hodgkin's disease, including 5 of 11 (45.4%) with nodular sclerosis and 1 of 3 (33%) with mixed cellularity. In these six patients, all biopsy sites were positive for both EBER1 and LMP. In the EBV-positive cases were analyzed the 3'-end of the EBV LMP1 gene in al sites of disease using polymerase chain reaction. In three patients all sites of disease had a 30-base pair deletion. In two patients, there was discordance between sites of disease, with LMP1 gene deletions in some sites and other sites with the LMP1 gene in the germline configuration. The results of this study demonstrate that EBV, when found in Hodgkin's disease, is detectable in all anatomic sites involved. The presence of the same 30-base pair deletion in the EBV LMP1 gene in all sites of disease in three patients suggests that the deletion occurred before dissemination and that all sites are clonally related. However, the discordance between anatomic sites in two patients suggests that LMP1 gene deletion may also occur as a later event, after dissemination. These results lend further support to the hypothesis that EBV plays a role in the pathogenesis of a subset of cases of Hodgkin's disease.

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Selected References

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  1. Boiocchi M., Dolcetti R., De Re V., Gloghini A., Carbone A. Demonstration of a unique Epstein-Barr virus-positive cellular clone in metachronous multiple localizations of Hodgkin's disease. Am J Pathol. 1993 Jan;142(1):33–38. [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Brousset P., Schlaifer D., Meggetto F., Bachmann E., Rothenberger S., Pris J., Delsol G., Knecht H. Persistence of the same viral strain in early and late relapses of Epstein-Barr virus-associated Hodgkin's disease. Blood. 1994 Oct 15;84(8):2447–2451. [PubMed] [Google Scholar]
  4. Chang K. L., Chen Y. Y., Shibata D., Weiss L. M. Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues, with a survey of normal and neoplastic tissues. Diagn Mol Pathol. 1992 Dec;1(4):246–255. [PubMed] [Google Scholar]
  5. Chittal S. M., Caverivière P., Schwarting R., Gerdes J., Al Saati T., Rigal-Huguet F., Stein H., Delsol G. Monoclonal antibodies in the diagnosis of Hodgkin's disease. The search for a rational panel. Am J Surg Pathol. 1988 Jan;12(1):9–21. doi: 10.1097/00000478-198801000-00002. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Delsol G., Brousset P., Chittal S., Rigal-Huguet F. Correlation of the expression of Epstein-Barr virus latent membrane protein and in situ hybridization with biotinylated BamHI-W probes in Hodgkin's disease. Am J Pathol. 1992 Feb;140(2):247–253. [PMC free article] [PubMed] [Google Scholar]
  8. Henle W., Henle G. Epstein-Barr virus-related serology in Hodgkin's disease. Natl Cancer Inst Monogr. 1973 May;36:79–84. [PubMed] [Google Scholar]
  9. 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]
  10. Khan G., Coates P. J., Kangro H. O., Slavin G. Epstein Barr virus (EBV) encoded small RNAs: targets for detection by in situ hybridisation with oligonucleotide probes. J Clin Pathol. 1992 Jul;45(7):616–620. doi: 10.1136/jcp.45.7.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Knecht H., Bachmann E., Brousset P., Sandvej K., Nadal D., Bachmann F., Odermatt B. F., Delsol G., Pallesen G. Deletions within the LMP1 oncogene of Epstein-Barr virus are clustered in Hodgkin's disease and identical to those observed in nasopharyngeal carcinoma. Blood. 1993 Nov 15;82(10):2937–2942. [PubMed] [Google Scholar]
  12. Knecht H., Bachmann E., Joske D. J., Sahli R., Eméry-Goodman A., Casanova J. L., Zilić M., Bachmann F., Odermatt B. F. Molecular analysis of the LMP (latent membrane protein) oncogene in Hodgkin's disease. Leukemia. 1993 Apr;7(4):580–585. [PubMed] [Google Scholar]
  13. Kvåle G., Høiby E. A., Pedersen E. Hodgkin's disease in patients with previous infectious mononucleosis. Int J Cancer. 1979 May 15;23(5):593–597. doi: 10.1002/ijc.2910230502. [DOI] [PubMed] [Google Scholar]
  14. Lukes R. J. Criteria for involvement of lymph node, bone marrow, spleen, and liver in Hodgkin's disease. Cancer Res. 1971 Nov;31(11):1755–1767. [PubMed] [Google Scholar]
  15. 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]
  16. Pinkus G. S., Lones M., Shintaku I. P., Said J. W. Immunohistochemical detection of Epstein-Barr virus-encoded latent membrane protein in Reed-Sternberg cells and variants of Hodgkin's disease. Mod Pathol. 1994 May;7(4):454–461. [PubMed] [Google Scholar]
  17. Sheibani K., Tubbs R. R. Enzyme immunohistochemistry: technical aspects. Semin Diagn Pathol. 1984 Nov;1(4):235–250. [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. 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]

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