AIDS and non-AIDS diffuse large B-cell lymphomas express different antigen profiles.
Based on gene expression profiling, diffuse large B-cell lymphomas arising in immunocompetent patients can be divided into germinal center and activated B-cell types. Since little is known about acquired immunodeficiency syndrome associated diffuse large B-cell lymphomas, we tested whether the protein expression of germinal center and activated B-cell markers differed between acquired immunodeficiency syndrome (AIDS) vs non-AIDS diffuse large B-cell lymphomas. We immunohistochemically stained tissue microarrays of 39 de novo diffuse large B-cell lymphomas: 12 AIDS associated and 27 non-AIDS, with germinal center (BCL6, CD10, CyclinH) and activated B-cell markers (MUM1, CD138, PAK1, CD44, BCL2). We scored each case for percent positive cells (0-19%=0; 20-49%=1; 50-100%=2). The activated B-cell and germinal center summation scores of each case were used as (x, y) coordinate data points to construct two-dimensional contour-frequency plots. The contour plot of non-AIDS diffuse large B-cell lymphomas showed two distinct clusters: a cluster with a high germinal center phenotype (cluster 1) and a cluster with a high activated B-cell phenotype (cluster 3). In contrast, the AIDS-related diffuse large B-cell lymphomas formed a single aggregate (cluster 2) (P=0.02, Fisher exact test). When the contour plots of the AIDS-related and the non-AIDS cases were superimposed, cluster 2 of the AIDS cases expressed an intermediate germinal center/activated B-cell phenotype compared to clusters 1 and 3 of the non-AIDS diffuse large B-cell lymphomas. Our results confirm that non-AIDS diffuse large B-cell lymphomas segregate into two groups with either germinal center or activated B-cell phenotype. We report the new finding that the AIDS status of the patient predicts the immunophenotype of the diffuse large B-cell lymphomas.
Madan
Rashna
R
Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10467, USA.
Gormley
Robert
R
Dulau
Alina
A
Xu
Dongsheng
D
Walsh
Daniel
D
Ramesh
K H
KH
Cannizaro
Linda
L
Tamas
Ecaterina F
EF
Kumar
Pankaj
P
Sparano
Joseph
J
LeValley
Aaron
A
Xue
Xiaonan
X
Bhattacharyya
Pritish K
PK
Ioachim
Harry L
HL
Ratech
Howard
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D050835:Interferon Regulatory Factors / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D016483:Lymphoma, AIDS-Related / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000032:analysis; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016019:Survival Analysis; D014178:Translocation, Genetic; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D019394:Ki-67 Antigen; D015260:Neprilysin; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human