[1367] Immunoglobulin Heavy Chains Help Discriminate between Germinal Center (GC)-Like vs. Non-GC-Like B-Cell Phenotype in Diffuse Large B-Cell Lymphoma (DLBCL)

Donghong Cai, Christine McMahon, John G Pizzolo, Howard Ratech. Albert Einstein Coll Med/Montefiore Med Ctr, Bronx, NY

Background: When normal B-cells respond to antigen, surface IgH progresses from antigen-naïve (AN; IgM plus IgD) to antigen-exposed (AE; IgM only) to class switched (CS) memory B-cell (IgG or IgA). Recently, it has been reported that the IgH isotype of the B-cell receptor (BCR), as determined by gene expression profiling (GEP), might be a surrogate for GC-like vs. non-GC-like subtype in DLBCL (Leukemia 2011; 25:681-688). We attempted to confirm this observation at the protein level by retrospectively studying the IgH class of the BCR in a large number of DLBCLs and in a control group of follicular lymphomas (FLs).
Design: Using multiparameter flow cytometry (FCM), we measured IgM, IgD, IgG, and IgA in 62 DLBCLs and in 73 FLs from 2002 to 2011 at Montefiore Med Ctr, Bronx, NY. We immunohistochemically stained tissue sections to determine CD10, bcl-6 protein and MUM1 in the DLBCLs in order to assign GC-like vs. non-GC-like B-cell phenotype (Blood 2004; 103:275-282).
Results: DLBCL or FL expressing surface IgM and/or IgD were binned in group MD and those expressing IgG or IgA were binned in group GA. The MD/GA ratio was not different between 62 DLBCLs and 73 FLs (2.76 vs. 2.90; χ² =0.04, p > 0.5). However, the IgH patterns of DLBCL and FL differed significantly: AE-like occurred more often in DLBCL and AN-like occurred more often in FL (Table 1. χ² =10.3, p = 0.006).

Table 1. Summary of IgH patterns in FL and DLBCL

Diagnosis	No. cases	AN-like	AE-like	CS
FL	73	42 (58%)	12 (16%)	19 (26%)
DLBCL	62	21 (34%)	24 (39%)	17 (27%)

Next, we tested if IgH patterns could discriminate between DLBCL GC-like vs. non-GC-like phenotypes. Table 2 shows that IgH pattern was highly significant (χ² =10.30, p = 0.006) because AN-like (IgM plus IgD) and AE-like (IgM only) occurred more often in DLBCL-non-GC-like but CS (IgG or IgA) occurred more often in DLBCL-GC-like.

Table 2. Summary of IgH patterns in DLBCL GC-like and non-GC-like

Phenotype	No. cases	AN-like	AE-like	CS
GC-like	35	8 (23%)	12 (34%)	15 (43%)
non-GC-like	27	13 (48%)	12 (45%)	2 (7%)

Conclusions: We report the new observation that AN-like vs. AE-like IgH patterns help distinguish FL vs. DLBCL. IgH, as determined by FCM, correlated with GC-like vs. non-GC-like phenotype in DLBCL. Our FCM data confirm the molecular results of a prior GEP study. We conclude that testing for surface IgH protein has potential for assigning GC-like vs. non-GC-like phenotype in DLBCL.
Category: Hematopathology

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 183, Tuesday Afternoon