Hodgkin cells accumulate mRNA 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 pathogenesis 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 investigate the expression of the bcl-2 oncogene in Hodgkin's disease both at the protein and mRNA level in correlation with the expression of the late membrane protein.


METHODS
Thirteen cases of all histologic types of Hodgkin's disease, six cases of chronic nonspecific lymphadenitis, three tonsils with follicular hyperplasia, seven cases of follicular small cleaved cell lymphoma, and six cases of follicular large cell lymphoma, were analyzed. We designed a novel digoxigenin-labeled oligonucleotide probe complementary to bcl-2 mRNA for nonisotopic in situ hybridization. Bcl-2 oncoprotein and late membrane protein expression 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 expression, however, varied from case to case, with the highest prevalence in the nodular sclerosing subtype, and showed no strict correlation with the late membrane protein. In our case, 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, while the bcl-2 protein expression was inhomogenous. In nodular lymphocyte predominant type, the bcl-2 mRNA and protein pattern is comparable to germinal center cells. This finding is a further argument for the germinal center cell origin of this type of Hodgkin's disease.
D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D004273:DNA, Neoplasm; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014763:Viral Matrix Proteins