Epstein-Barr virus-latent gene expression and tumor cell phenotype in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Correlation of lymphoma phenotype with three distinct patterns of viral latency.
We investigated 49 acquired immunodeficiency syndrome-related lymphomas (ARLs) for Epstein-Barr virus (EBV) by Southern blotting and in situ hybridization and, in positive cases, used cryostat immunohistology to compare EBV-latent gene expression (EBV encoded small RNA-1 [EBER-1], EBV nuclear antigen-2 [EBNA-2], latent membrane protein-1 [LMP-1] and host cell immunophenotype (CD11a, CD18, CD54, CD58, CD21, CD23, CD30, CD39, CDw70, immunoglobulin) patterns with those reported in other EBV infections. EBV+ immunoblast-rich/large cell ARLs (n = 22) showed three patterns of latency: broad (EBER+EBNA-2+/LMP-1+; n = 9), reminiscent of a lymphoblastoid cell line phenotype; restricted (EBER+/EBNA-2-/LMP-1-; n = 6), similar to endemic Burkitt's lymphoma; and intermediate (EBER+/EBNA-2-/LMP-1+; n = 7), a pattern rarely described in vitro but seen in certain EBV-related malignancies. EBNA-2 expression was associated with extranodal lymphomas. EBV+ Burkitt-type ARLs (n = 11) usually showed the restricted latency pattern (n = 8), but some expressed the intermediate form (n = 3). Adhesion (CD54, CD58) and activation (CD30, CD39, CDw70) molecule expression varied with morphology (immunoblast-rich/large cell versus Burkitt-type), but was not independently correlated with EBV-positivity. CD30 and LMP-1 expression were associated. ARLs show heterogeneity regarding both the presence of EBV and latency pattern. Comparison of these phenotypically distinct lymphoma groups with known forms of EBV infection provides clues to their possible pathogenesis.
Hamilton-Dutoit
S J
SJ
Laboratory of Immunohistology, Aarhus University Hospital, Denmark.
Rea
D
D
Raphael
M
M
Sandvej
K
K
Delecluse
H J
HJ
Gisselbrecht
C
C
Marelle
L
L
van Krieken
H J
HJ
Pallesen
G
G
D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000378:metabolism*; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016483:Lymphoma, AIDS-Related / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012269:Ribosomal Proteins; D014763:Viral Matrix Proteins / Q000378:metabolism*; D017735:Virus Latency
D000956:Antigens, Viral; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D009856:Oncogene Proteins, Viral; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D014763:Viral Matrix Proteins; C067169:RPL22 protein, human