Discrepancies in Epstein-Barr virus association at presentation and relapse of classical Hodgkin's disease: impact on pathogenesis.
BACKGROUND
Though Epstein-Barr virus (EBV) has been linked to classical Hodgkin's disease (cHD), only a proportion of cHD cases show EBV-association. While there has been evidence to suggest a crucial role for EBV in the early phase of cHD evolution, we are unclear whether continued presence of EBV is essential for the maintenance of the neoplasm. We have addressed this issue by investigating the EBV-association in paired samples of cHD obtained at presentation and relapse.


METHODS
We have analysed lymph node biopsy samples from 23 cases of cHD at presentation and relapse. In situ hybridization with EBER-1 probe and immunostaining with anti latent membrane protein-1 (LMP-1) antibody was performed on the paraffin sections. PCR for EBNA 3C gene was performed for EBV subtype analysis on the DNA extracted from paraffin sections.


RESULTS
EBV-association was documented in both the presentation and relapse samples of 14 cases. One case showed loss of EBV-association at relapse. PCR analysable DNA was obtained from both presentation and relapse samples in four of the EBV-associated cases. The EBNA 3C amplimer corresponded to type A strain of EBV in all the samples.


CONCLUSIONS
Loss of EBV-association between presentation and relapse seen in one case implies a hit and run mechanism in EBV-induced lymphomagenesis. Though EBV may be essential early in the evolution of cHD, it may not be required for maintenance of the neoplastic clone. Our study also brings out a speculation that a proportion of EBV-negative cHD could represent loss of EBV in the tumour prior to clinical presentation. Alternatively, an unidentified lymphotropic virus other than EBV might play a pathogenetic role in EBV-negative cHD.
Nerurkar
A Y
AY
Department of Pathology, Tata Memorial Hospital, Mumbai, India.
Vijayan
P
P
Srinivas
V
V
Soman
C S
CS
Dinshaw
K A
KA
Advani
S H
SH
Magrath
I
I
Bhatia
K
K
Naresh
K N
KN
D002051:Burkitt Lymphoma / Q000503:physiopathology / Q000821:virology*; D004273:DNA, Neoplasm; D004854:Herpesvirus 4, Human; D006689:Hodgkin Disease / Q000503:physiopathology / Q000821:virology*; D006801:Humans; D017403:In Situ Hybridization; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D014763:Viral Matrix Proteins / Q000032:analysis
D004273:DNA, Neoplasm; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins