1. ¹Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA
2. ²Department of Pathology, Lenox Hill Hospital, New York, NY, USA
3. ³Department of Oncology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA
4. ⁴Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
5. ⁵Department of Pathology, Hackensack Medical Center, Hackensack, NJ, USA

Correspondence: Dr H Ratech, MD, Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, 111 E 210th Street, Silver Zone, North 4, Bronx, NY 10467, USA. E-mail: hratech@montefiore.org

^*These three authors equally contributed to this work.

Received 15 June 2005; Revised 11 August 2005; Accepted 11 August 2005; Published online 27 January 2006.

Abstract

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.