Germinal Center and Activated B-Cell Profiles Separate Burkitt Lymphoma and Diffuse Large B-Cell Lymphoma in AIDS and Non-AIDS Cases

Abstract

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.

Abnormal AP-1 protein expression in primary cutaneous B-cell lymphomas

“…In addition, expression of CCND1, a downstream protein regulated by AP‐1, was identified in most PCMZL, PCFCL, PCLBCL‐LT and unspecific PCBCL cases consistent with previous studies showing increased CCND1 gene expression in B‐cell lymphoma and leukaemia, 18–20 further implicating its role in the pathogenesis of B‐cell malignancy including PCBCL. Although αPAK, an upstream protein of AP‐1, has been regarded as one of the activated B‐cell markers, 21,22 in this study αPAK protein expression was noted not only in a proportion of PCBCL but also in MM and psoriasis, suggesting its diverse biological functions in cell proliferation and malignant transformation as revealed by previous reports 23–26 . However, JUNB protein expression was absent in all PCBCL cases tested, further consolidating previous studies revealing copy number loss and reduced gene expression of JUNB in PCBCL 11,12 and other B‐cell lymphoma and leukaemia 13,14 .…”

Revealing Global Regulatory Perturbations across Human Cancers

“…cluster 8 for “antigen processing” and cluster 39 for “cytokine receptor activity”). The higher expression of lymphocyte-specific pathways in DLBCL has been previously shown by employing immunohistochemical analysis, and revealed the overabundance of B cell activated markers (Gormley et al, 2005). …”

Frequent expression of multiple myeloma 1/interferon regulatory factor 4 in Burkitt lymphoma

“…In studies of DLBCL and BL subjected to immunophenotyping panels, including markers of GC (CD10, bcl-6) and activated-B-cells (ABC) (bcl-2, CD44, CD138, MUM1) type differentiation, hierarchical clustering has yielded two major groups: one with a high CG/low ABC score, that tends to include the lymphomas morphologically interpreted as BL and a second group with a low GC/high ABC score that includes DLBCL. However there is a continuum of expression of GC-markers and ABC-markers, with no distinct separation of the two groups, suggesting there may be a true biological continuum between BL and DLBCL (23, 24). Similarly, all BL harbor a C-MYC translocation, but 5-15% of DLBCL also may have a C-MYC rearrangement (18, 19, 23).…”

“…Expression of bcl-6 is restricted to GC-B-cells (14), and MUM1 marks the final step of intra-GC differentiation and subsequent early post-GC events. Bcl-6 expression in BL has been observed in 70 to 100% of pediatric cases and 70 to 82% of adult cases (20, 24). …”