Los virus herpes humanos 4 (virus de Epstein-Barr) y 6 (HHV-6) en las enfermedades de Hodgkin y de Kikuchi, y su relación con proliferación y apoptosis / Human herpes viruses 4 (viruses Epstein-Barr) and 6 (HHV-6) in the Hodgkin's and Kikuchi's diseases, and its relationship with proliferation and apoptosis

ABSTRACT

Background: Epstein-Barr virus/EBV and HHV-6 are frequently found in Hodgkin's disease (HD) and ­to a certain extent­ in Kikuchi-Fujimoto's disease (KFD). Both viruses are apparently related to proliferative and/or apoptotic processes as represented by HD or KFD respectively. Objective: To correlate frequency and location of antigen and DNA expression of both viruses in HD or KFD tissue sections in relation to markers for cell proliferation and apoptosis. Design: Archival lymph node biopsies from 84 patients from the Hospital General de Mexico and 26 from the Clinic of the University of Cologne, Germany with HD and 14 with KFD were investigated immunhistologically for viral antigen expression (EBV LMP-1 HHV-6 gp110/60), Ki67/PCNA marker for proliferation (MIB1)/p53 and WAF1 for apoptosis. Viral ADN was shown by in situ hybridization. Apoptosis was determined by ISEL and TUNEL techniques. Results: HD is frequently infected by both EBV and HHV-6 while KFD tends to be infected only by HHV-6. EBV and HD is present in HD cells and Reed-Sternberg cells, HHV-6 preferentially in lymphocytes and in histiocytes in both HD and in KFD. Proliferation marker is found in both diseases. Apoptosis is demonstrated preferentially in KFD and to a lesser extent also in HD. Conclusion: Although EBV and HHV-6 may not be openly oncogenic in HD and KFD, they may well influence the course of the disease. Dual infection in HD appears to support proliferative processes,i.e. a redominance of EBV effects. Single infection with HHV-6 in KFD instead appears to favor an apoptotic course. These effects are ­according to the literature­ possibly cytokine-mediated.