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

Abstract

This study of 52 Swiss patients with Hodgkin's disease (HD), including 17 cases with a high content of Sternberg-Reed (SR) and Hodgkin (H) cells, was performed to determine the percentage of cases harboring Epstein-Barr virus (EBV) DNA and/or clonal rearrangements of Ig and T- cell antigen receptor (TcR) genes in diagnostic lymph node biopsies. Special attention was drawn to the heavily infiltrated cases to detect a possible relationship between clonality and EBV DNA identification. EBV DNA was detected by the polymerase chain reaction (PCR) using three different sets of specific primers. The viral origin of the amplification products was confirmed by hybridization with a radiolabeled internal probe or demonstration of a specific Sma I restriction site. Genomic rearrangement of Ig and TcR genes was studied by Southern blot analysis. EBV DNA was identified by PCR in 38 of 48 cases (79%). Clonal rearrangements were identified in only 4 of 52 cases (Ig genes) and were independent of the degree of infiltration by SR cells and the presence of EBV DNA. The absence of EBV DNA in three cases with numerous SR cells (only one of them showed clonal rearrangement) and the presence of only a few viral copies in four further cases with numerous SR cells (semiquantitative analysis of viral DNA by PCR was performed in 26 EBV-positive cases) suggests that this virus is modulating rather than an etiologic agent in a considerable proportion of HD cases.

Epstein-Barr virus-associated Hodgkin's disease: Epidemiologic characteristics in international data

“…For each patient included in their publications or tested subsequently, authors were asked to contribute data on age at diagnosis, sex, ethnicity, histologic subtype, clinical stage, year of diagnosis, country of residence at diagnosis, human immunodeficiency virus (HIV) status and outcome of EBER and/or LMP-1 tests. Of the 23 research groups approached, 12 submitted case information [Jarrett et al (Armstrong et al, 1992; Brousset et al Delsol et al, 1992Delsol et al, , 1993; Pallesen et al (Pallesen et al, 1991a and b;Vestlev et al, 1992;Zhou et al, 1993;Levine et al, 1994); Gulley et al (1994); Khan et al (Khan et al, 1992O'Grady et al (1994); Hummel et al (1992); Ambinder et al (1993); Preciado et al (Preciado et al, 1995a and b;Knecht et al (Knecht et al, 1991;Joske et al, 1992); Chan et al (1995); and Claviez et al (1994)]. This was augmented with one case series published in its entirety (Zarate-Osorno et al, 1995) and one unpublished series.…”

The association between epstein‐barr virus and chinese hodgkin's disease

“…The sensitivity of EBV detection is even greater if the polymerase chain reaction (PCR) is used, and EBV genomes have been reported in tumour tissues from 40% to 86% of HD cases when this technique was used (Herbst et al, 1990;Knecht et al, 1991;Masih et al, 1991;Wright et al, 1991;Armstrong et al, 1992). However, methods such as PCR and Southern blotting, which are based on tissue extracts, cannot identify the cellular source of a given nucleic acid.…”

Epstein–Barr virus‐positive aggressive lymphoma as a consequence of immunosuppression after multiple salvage treatments for follicular lymphoma

“…Immunohistochemical analysis was performed on formalinfixed, paraffin-embedded lymphoma lesions. EBV investigations on formalin-fixed, paraffin-embedded tissue sections were performed using: (1) immunohistochemical analysis with monoclonal antibodies to LMP1 and EBNA2 (Dako); (2) in situ hybridization (ISH) using fluorescein-labelled oligonucleotides complementary to EBER 1 and 2 (Dako); (3) PCR amplification of the BamW region of the EBV genome (Knecht et al, 1991). B-cell clonality was assessed using PCR analysis of IgH gene rearrangements, using a sense primer directed at IgH variable region consensus sequence, framework III (FR3A), and an antisense primer directed at a consensus sequence at the IgH joining regions (VLJH), according to previously described protocols (Fo Èdinger et al, 1999).…”