Apoptosis-related genes and proteins in Hodgkin's disease.
During recent years it has become increasingly evident that L&H cells in nodular 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 and there are also indications that genes involved in programmed cell death (apoptosis) may be implicated. In this study, the expression of four apoptosis-related proteins (bcl-2, bcl-x, bax and p53) in 53 cases of HD was examined 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 (14/19, 74%) than in null (7/29, 24%) type HD. The H-RS cells were bcl-2-positive in 19/53 (36%), bcl-x-positive in 17/53 (32%), bax-positive in 1/53, and 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 bcl-2, bcl-x and p53 in tumorigenesis. The pathogenesis is not known at this stage.
Lauritzen
A F
AF
Department of Pathology, Herlev Hospital, University of Copenhagen, Denmark.
Møller
P H
PH
Nedergaard
T
T
Guldberg
P
P
Hou-Jensen
K
K
Ralfkiaer
E
E
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D004854:Herpesvirus 4, Human / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D011817:Rabbits; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D014763:Viral Matrix Proteins / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D015703:Antigens, CD; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein