Abstract
The recent detection of clonal episomes of Epstein-Barr virus (EBV) in a significant proportion of Hodgkin's disease (HD) cases has suggested a re-evaluation of the possible pathogenetic role of EBV in the development of the disease. Here we report that in two EBV-positive HD, arisen in human immunodeficiency virus-1-infected drug users, a unique episomal EBV genome was detected in multiple metachronous HD lesions of each patient. These findings demonstrated that the same EBV-positive cellular clone was present in multiple localizations of HD as well as in specimens taken at different times. Combined in situ hybridization and immunohistological analyses evidenced EBV genome and EBV-encoded latent membrane protein-1 on Reed-Sternberg cells. Therefore, the data strongly support the possibility of a causal role for EBV in the pathogenesis of HD.
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- Alexander F. E. Clustering and Hodgkin's disease. Br J Cancer. 1990 Nov;62(5):708–711. doi: 10.1038/bjc.1990.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Boiocchi M., De Re V., Dolcetti R., Carbone A., Scarpa A., Menestrina F. Association of Epstein-Barr virus genome with mixed cellularity and cellular phase nodular sclerosis Hodgkin's disease subtypes. Ann Oncol. 1992 Apr;3(4):307–310. doi: 10.1093/oxfordjournals.annonc.a058187. [DOI] [PubMed] [Google Scholar]
- Boiocchi M., De Re V., Dolcetti R., Volpe R., Gloghini A., Tavian M., Viel A., Maestro R., Carbone A. Pathogenesis of malignant lymphomas in intravenous drug-abuser, HIV-infected patients. Cancer Detect Prev. 1990;14(6):661–668. [PubMed] [Google Scholar]
- Browne H., Smith G., Beck S., Minson T. A complex between the MHC class I homologue encoded by human cytomegalovirus and beta 2 microglobulin. Nature. 1990 Oct 25;347(6295):770–772. doi: 10.1038/347770a0. [DOI] [PubMed] [Google Scholar]
- Carbone A., De Re V., Gloghini A., Volpe R., Tavian M., Tirelli U., Monfardini S., Boiocchi M. Immunoglobulin and T cell receptor gene rearrangements and in situ immunophenotyping in lymphoproliferative disorders. Virchows Arch A Pathol Anat Histopathol. 1989;414(3):223–230. doi: 10.1007/BF00822026. [DOI] [PubMed] [Google Scholar]
- Carbone A., Gloghini A., Volpe R., Boiocchi M. Anti-vimentin antibody reactivity with Reed-Sternberg cells of Hodgkin's disease. Virchows Arch A Pathol Anat Histopathol. 1990;417(1):43–48. doi: 10.1007/BF01600108. [DOI] [PubMed] [Google Scholar]
- Carbone A., Manconi R., Poletti A., Tirelli U., De Paoli P., Santini G., Diodato S., Manconi P. E., Grigoletto E., Santi L. Lymph node immunohistology in intravenous drug abusers with persistent generalized lymphadenopathy. Arch Pathol Lab Med. 1985 Nov;109(11):1007–1012. [PubMed] [Google Scholar]
- 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]
- Dawson C. W., Rickinson A. B., Young L. S. Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature. 1990 Apr 19;344(6268):777–780. doi: 10.1038/344777a0. [DOI] [PubMed] [Google Scholar]
- Dolcetti R., De Re V., Viel A., Pistello M., Tavian M., Boiocchi M. Nuclear oncogene amplification or rearrangement is not involved in human colorectal malignancies. Eur J Cancer Clin Oncol. 1988 Aug;24(8):1321–1328. doi: 10.1016/0277-5379(88)90223-4. [DOI] [PubMed] [Google Scholar]
- Fåhraeus R., Rymo L., Rhim J. S., Klein G. Morphological transformation of human keratinocytes expressing the LMP gene of Epstein-Barr virus. Nature. 1990 May 31;345(6274):447–449. doi: 10.1038/345447a0. [DOI] [PubMed] [Google Scholar]
- Gutensohn N., Cole P. Childhood social environment and Hodgkin's disease. N Engl J Med. 1981 Jan 15;304(3):135–140. doi: 10.1056/NEJM198101153040302. [DOI] [PubMed] [Google Scholar]
- Gutensohn N., Cole P. Epidemiology of Hodgkin's disease. Semin Oncol. 1980 Jun;7(2):92–102. [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Lewis F. A., Griffiths S., Dunnicliff R., Wells M., Dudding N., Bird C. C. Sensitive in situ hybridisation technique using biotin-streptavidin-polyalkaline phosphatase complex. J Clin Pathol. 1987 Feb;40(2):163–166. doi: 10.1136/jcp.40.2.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Murray R. J., Wang D., Young L. S., Wang F., Rowe M., Kieff E., Rickinson A. B. Epstein-Barr virus-specific cytotoxic T-cell recognition of transfectants expressing the virus-coded latent membrane protein LMP. J Virol. 1988 Oct;62(10):3747–3755. doi: 10.1128/jvi.62.10.3747-3755.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Uccini S., Monardo F., Ruco L. P., Baroni C. D., Faggioni A., Agliano A. M., Gradilone A., Manzari V., Vago L., Costanzi G. High frequency of Epstein-Barr virus genome in HIV-positive patients with Hodgkin's disease. Lancet. 1989 Jun 24;1(8652):1458–1458. doi: 10.1016/s0140-6736(89)90171-2. [DOI] [PubMed] [Google Scholar]
- Vianna N. J., Greenwald P., Davies J. N. Extended epidemic of Hodgkin's disease in high-school students. Lancet. 1971 Jun 12;1(7711):1209–1211. doi: 10.1016/s0140-6736(71)91719-3. [DOI] [PubMed] [Google Scholar]
- Wang D., Liebowitz D., Kieff E. An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell. 1985 Dec;43(3 Pt 2):831–840. doi: 10.1016/0092-8674(85)90256-9. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Young L., Alfieri C., Hennessy K., Evans H., O'Hara C., Anderson K. C., Ritz J., Shapiro R. S., Rickinson A., Kieff E. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. doi: 10.1056/NEJM198910193211604. [DOI] [PubMed] [Google Scholar]