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 Ho dgkin'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 ear ly phase of cHD evolution, we are unclear whether continued presence of EBV is essential for the maintenance of the neoplasm. We have addressed this i ssue by investigating the EBV-association in paired samples of cHD obtained at presentation and relapse. Materials and methods: We have analysed lymph node biopsy samples from 23 c ases of cHD at presentation and relapse. In situhybridization with EBER-1 p robe and immunostaining with anti latent membrane protein-1 (LMP-1) antibod y was performed on the paraffin sections. PCR for EBNA 3C gene was performe d for EBV subtype analysis on the DNA extracted from paraffin sections. Results: EBV-association was documented in both the presentation and relaps e 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 t ype A strain of EBV in all the samples. Conclusion: Loss of EBV-association between presentation and relapse seen i n 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 re quired 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 unident ified lymphotropic virus other than EBV might play a pathogenetic role in E BV-negative cHD.