High prevalence of a 30-base pair deletion in the Epstein-Barr virus (EBV)latent membrane protein 1 gene and of strain type B EBV in Mexican classical Hodgkin's disease and reactive lymphoid tissue

Depending on geographic location and patient age Hodgkin's disease (HD) is associated with Epstein-Barr virus (EBV), mostly type A EBV, in 20% to 100% . The highest prevalence occurs in children of developing countries, Molecu lar analysis of the oncogene coding for the latent membrane protein 1 (LMP- 1) revealed a 30-base pair (bp) deletion in up to 46% of EBV-positive HD. W e investigated the presence of EBV in a series of Mexican classical HD (n = 57) and reactive lymphoid tissues (n = 20) from a private and a public hos pital with special emphasis on the prevalence of the 30-bp deletion and the type of EBV. EBV infection was analyzed at the cellular level by Epstein-B arr encoded early RNA transcripts (EBER) in situ hybridization (ISH) and by LMP-1 protein immunohistochemistry (MC). Molecular analysis of the LMP-1 g ene configuration was performed by polymerase chain reaction (PCR) with pri mers spanning the site of the deletion and subsequent Southern and/or dot b lot hybridization using wild-type and deletion-specific probes. The prevale nce of type A and type B EBV was investigated by PCR-analysis for divergenc e in the coding region of Epstein-Barr nuclear antigen (EBNA)-2. EBV was de tected in Hodgkin- and Reed-Sternberg cells (H-RS) by LMP-1 IHC and/or EBER ISH in 35/57 (61%) Mexican HD including 18/32 (56%) with nodular sclerosis , 15/20 (75%) with mixed cellularity and 2/4 (50%) with lymphocyte depletio n. In addition, LMP-1 gene sequences were detected by PCR in 9 cases of HD without LMP/EBER expression by H-RS cells and in 17/20 (85%) reactive lymph nodes, supposedly originating from rare latently infected B cells. Surpris ingly, the 30-bp LMP-1 deletion was found in 28/35 (80%) EBV-positive HD. T his deletion, however, was also found in all 9 (100%) HD with H-RS cells ne gative for EBV and in 10/17 (59%) reactive lymph nodes. Thus, the overall L MP-1 del prevalence in reactive tissue is 73% (19/26). Typing of EBV was su ccessful in 26 cases of EBV-positive HD, 10 of these were infected by type B EBV (38%). Of the reactive lymphoid tissue, 9 (47%) were infected by type A and 10 (53%) by type B; All 20 cases (100%) associated with type B, whet her neoplastic or reactive, displayed the LMP-1 del variant compared with 1 8/25 (72%) infected by type A EBV. To our knowledge, this is the highest in cidence for both the LMP-1 deletion variant and the infection by type B EBV in HD reported so far worldwide. Our data suggest that EBV infection contr ibutes to the pathogenesis of the majority of Hodgkin's disease cases in Me xico. The specific tumorigenic role of the LMP-1 deletion variant, however, is doubtful with regard to its high frequency in nonneoplastic lesions. Mo reover, type B infection frequently occurs in Mexican HD and reactive lymph oid tissue and is consistently associated with the deletion variant pointin g to a pathogenetic role of this combined genotype. Copyright (C) 1999 by W .B. Saunders Company.