Apoptosis-related genes and proteins in Hodgkin's disease

During recent years it has become increasingly evident that L&H cells in no dular lymphocytic predominance (LP) Hodgkin's disease (HD) and Hodgkin and Reed-Sternberg (H-RS) cells in approximately half the cases of classical HD originate from B-lymphocytes, and that H-RS cells in most of the remaining cases of classical HD express a null phenotype. The pathogenesis of HD is unknown. An association with Epstein-Barr virus (EBV) has been suggested an d there are also indications that genes involved in programmed cell death ( apoptosis) may be implicated. In this study, the expression of four apoptos is-related proteins (bcl-2, bcl-x, bar and p53) in 53 cases of HD was exami ned and the data were correlated with the genotype, the EBV status and the phenotype (B, T or null) of the neoplastic cells. The H-RS cells expressed a B-cell phenotype in 3/3 cases of nodular LP and in 19/ 50 (38%) cases of classical HD. The remaining cases showed a null-cell phenotype in 29/50 (58 %) and a T-cell phenotype in 2/50 (4%). EBV was more often positive in B (1 4/19, 74%) than in null (7/29, 24%) type HD. The H-RS cells were bcl-2-posi tive in 19/53 (36%), bcl-x-positive in 17/53 (32%), bax-positive in 1/53, a nd p53-positive in 41/53 (77%) cases. No relationship was found between bcl -2 expression and EBV status, or between bcl-2 and bcl-x expression. A t(14 ;18) translocation was seen in 2 of 34 cases. P53 point mutations were not detected. Our findings indicate that nodular LP and classical HD originate from B-cells in a high proportion of cases. They also suggest a role for bc l-2, bcl-x and p53 in tumorigenesis. The pathogenesis is not known at this stage.