HODGKIN CELLS ACCUMULATE MESSENGER-RNA FOR BCL-2

BACKGROUND: The bcl-2 oncogene is able to prevent cells from apoptosis . Overexpression of the bcl-2 protein seems to be important for the pa thogenesis of follicular center cell lymphomas, in which both protein and mRNA usually show high levels. In addition, the expression of the Epstein-Barr virus-encoded late membrane protein up-regulates the bcl- 2 protein in cell lines. The aim of the current study was to investiga te the expression of the bcl-2 oncogene in Hodgkin's disease both at t he protein and mRNA level in correlation with the expression of the la te membrane protein. EXPERIMENTAL DESIGN: Thirteen cases of all histol ogic types of Hodgkin's disease, six cases of chronic nonspecific lymp hadenitis, three tonsils with follicular hyperplasia, seven cases of f ollicular small cleaved cell lymphoma, and six cases of follicular lar ge cell lymphoma, were analyzed. We designed a novel digoxigenin-label ed oligonucleotide probe complementary to bcl-2 mRNA for nonisotopic i n situ hybridization. Bcl-2 oncoprotein and late membrane protein expr ession were determined by immunohistochemistry. The presence of the 14 ;18 translocation was analyzed by PCR for the major breakpoint region. RESULTS: The main finding was that, irrespective of subtype, the vast majority of Hodgkin cells express abundant bcl-2 mRNA. Oncoprotein ex pression, however, varied from case to case, with the highest prevalen ce in the nodular sclerosing subtype, and showed no strict correlation with the late membrane protein. In our cases, no 14;18 translocation could be found in Hodgkin's disease. CONCLUSIONS: Hodgkin cells in all types of Hodgkin's disease demonstrated high levels of bcl-2 mRNA,whi le the bcl-2 protein expression was inhomogenous. In nodular lymphocyt e predominant type, the bcl-2 mRNA and protein pattern is comparable t o germinal center cells. This finding is a further argument for the ge rminal center cell origin of this type of Hodgkin's disease.