Apoptosis, proliferative activity and Bcl-2 expression in Epstein-Barr-virus-positive non-Hodgkin's lymphomas.
In order to clarify the effects of Epstein-Barr virus (EBV) infection on apoptosis and proliferative activity of non-Hodgkin's lymphoma, 135 Japanese lymphoma cases were investigated for the presence of viral RNA and its correlation with bcl-2 protein (Bcl-2) expression. In addition, the role of EBV in lymphoma-genesis was also studied in terms of EBV genotyping and specific deletion in the gene for the latent membrane protein 1 (LMP-1). EBER-1 RNA in situ hybridization revealed EBV in 18 cases (13.3%), comprising 12 of 44 T cell (27.3%) and 6 of 91 B cell (6.6%) lymphomas. Type A EBV was found in all 18 cases (100%), and 17 of the 17 (100%) evaluable cases showed a 30-bp deletion within the 3' end of LMP-1. Comparison of apoptotic indices (AI), assessed by DNA nick-end labelling, and proliferative activity, estimated in terms of Ki-67 labelling and mitotic indices (KI and MI), demonstrated an overall correlation among AI, KI and MI increases in association with Bcl-2 negativity, indicating a close relation between apoptosis and proliferation. EBV-positive cases showed significantly elevated AI values, independent of Bcl-2 positivity, with no change in KI and MI. These results indicate that EBV in Japanese non-Hodgkin's lymphomas is exclusively of type A with a specific deletion in LMP-1 and that it tends to be present in T cell lymphomas. Moreover, EBV up-regulates apoptosis without any relation to Bcl-2 expression and exerts only minor effects on proliferation.
Takano
Y
Y
Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Saegusa
M
M
Masuda
M
M
Mikami
T
T
Okayasu
I
I
D017209:Apoptosis; D002455:Cell Division; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D017403:In Situ Hybridization; D007564:Japan; D019394:Ki-67 Antigen / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008938:Mitosis; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics
C099537:Epstein-Barr virus encoded RNA 1; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral