Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
What role does EBV play in the pathogenesis of Hodgkin's disease? (Meeting abstract).
Lymphoma: the next questions. April 2-4, 1992, Orlando, FL, 1992.. Unique Identifier : AIDSLINE ICDB/93690620 Weiss LM; Div. of Pathology, City of Hope Natl. Medical Center, Duarte, CA
Abstract:
A relationship between EBV and Hodgkin's disease (HD) had been long hypothesized. Patients (pts) with a history of EBV-associated infectious mononucleosis had an increased risk of HD over control populations. In 1987, we reported the presence of EBV genomes in approx 20% of cases of HD, using slot-blot and Southern blot hybridization. With a probe directed against the EBV terminus, we demonstrated that the EBV genome was present in a monoclonal population of cells. Using relatively insensitive in situ hybridization methods, we were able to localize the EBV genomes to within Reed-Sternberg (RS) cells and variants, and not within the reactive lymphocytes or other cellular elements. The percentage of positive cases, approx 20-30%, was similar to that obtained in Southern blot studies. Studies utilizing the polymerase chain reaction (PCR) demonstrated a higher incidence of EBV genomes in HD (50-80% of cases). Did the EBV DNA detected by PCR represent EBV exclusively from within RS cells or was EBV from other cells also being detected? Indeed, the latter possibility seemed probable, as these same PCR studies identified EBV DNA in from 0 to 43% of 'normal' lymph nodes. Utilizing a highly sensitive in situ hybridization method which uses an oligonucleotide probe directed against EBER-1 RNA, a transcript copied up to 10(6)-10(7) times in latently infected cells. Applying this technology to HD, we have identified EBV RNA in RS cells in approx 50% of cases of classical HD; in almost all of these positive cases, all or virtually all of the RS cells were positive. In addition, we have been able to localize EBV RNA to occasional lymphocytes in almost 90% of cases, identifying the probable source for the high percentages obtained in the PCR studies. Most of these lymphocytes are CD20-expressing (B lineage) lymphocytes with some CD43-expressing (T lineage) lymphocytes. Immunohistochemical studies have added significantly to our understanding of the EBV infection in HD. RS cells in EBV-positive cases have been shown to express EBV latent membrane protein. In contrast, RS cells lack the proteins EBNA2, gp350/250, viral capsid antigen, and early membrane antigen, and only a minority of cases express BZLF1 protein. These findings are consistent with a latent infection, with an abortive lytic infection possibly present in a small number of cases. EBV is found in HD most frequently in the mixed cellularity subtype and has seldom been reported in lymphocyte predominance type. One study noted an increased percentage of EBV positivity in pts under 15 or over 50 yr, as opposed to pts between 15 and 50. A very high incidence of EBV positivity has been identified in HD occurring in HIV-infected pts. No significant difference in clinical stage or prognosis was found between EBV-positive and negative pts. Studies performed to date provide strong evidence for an association of EBV with HD in approx 50% of cases. It is important to stress that in about 50% of cases of HD, RS cells have been shown to not contain EBV. None of the studies have provided compelling evidence for a specific role for EBV in either the etiology or pathogenesis of HD. Additional work needs to be performed in EBV-positive cases, to define a role for EBV, as well as in EBV-negative cases, to identify possible etiologic factors such as other infectious agents.
Keywords: Adolescence Adult Blotting, Southern DNA, Viral/ANALYSIS Genome, Viral Herpesvirus 4, Human/GENETICS/*PATHOGENICITY Hodgkin's Disease/*MICROBIOLOGY Human Immunohistochemistry Middle Age Oligonucleotide Probes Polymerase Chain Reaction Reed-Sternberg Cells/MICROBIOLOGY RNA, Viral/ANALYSIS ABSTRACT 930830
M9380840
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
