Epstein-Barr virus association in classical Hodgkin's disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed-Sternberg cells

Background: Most Epstein-Barr virus (EBV) associated lymphoproliferative di sorders have high proliferation indices. However, classical Hodgkin's disea se (cHD) is heterogeneous, with respect to proliferation index of the Reed- Sternberg cell (RS cell), and EBV association. Hence, we investigated wheth er cHD with and without EBV-association differ with respect to the prolifer ation index of the RS cells. Further we investigated whether this would hav e a bearing on patients survival. Patients and methods: We investigated 110 cases of cHD for: a) EBV associat ion by immunohistochemical demonstration of EBV-latent membrane protein-1 a nd EBV encoded nuclear RNA 1 by mRNA in situhybridisation; b) Proliferating cell nuclear antigen (PCNA) expression in the RS cells. Results: EBV association was noted in 86 of 110 cases (78%). Higher PCNA ex pression (P = 0.004) and younger age (P = 0.001) correlated independently w ith EBV association. The 10 year relapse free survival (RFS) of EBV+ and EB V- patients were 60% and 44%, respectively (P = 0.03). The 10 year overall survival (OS) of EBV+ and EBV- patients were 85% and 64%, respectively (P = 0.03). EBV association maintained its significant impact on RFS and OS wit hin Cox proportional hazard model. Conclusions: Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in c ell cycle. Hence, RS cells in EBV associated cHD would be more responsive t o chemotherapy and radiotherapy associated DNA damage. Thus, EBV-associatio n provides survival advantage to cHD patients treated with standard chemoth erapy and radiotherapy protocols.