Down Regulation of Oct-2 Expression in Non-Secretory Plasma Cell Myeloma Is Associated with Decreased Immunoglobulin Transcription.
Silver Daniel, Xia Chen, Edward Poje, Elizabeth Hyjek, James Vardiman. University of Chicago, IL; William Beaumont Hospital, Troy, MI; Memorial Medical Center, Springfield, IL
Background: Nonsecretory plasma cell myeloma (NS-PCM) is a rare form of plasma cell myeloma (PCM). We recently encountered 2 cases of NS-PCM with lymphocyte-like morphology (LLPCM), CD20+, no cytoplasmic kappa or lambda mRNA by in-situ hybridization and no paraprotein or increased immunoglobulin (Ig) by protein electrophoresis/immunofixation. FISH demonstrated IgH@/CCDN1 in one case and +11q13 and rearranged IGH@ in the other. We hypothesized that the lack of Ig production in NS-LLPCM may be associated with down regulation of transcription factors Oct-2 and OBF-1 which regulate Ig gene transcription by binding to a cis-regulatory octamer motif found in Ig gene variable region promoters and heavy chain intronic enhancers and that are necessary for proper Ig gene expression in B-cells. Due to limited published data regarding Oct-2 or OBF-1 expression in PCM we compared findings in NS-LLPCM to PCM with paraproteins, lymphoplasmacytic lymphoma (LPL) and reactive plasmacytoses (RP).
Design: Two cases of NS-LLPCM, 20 cases of PCM with paraprotein production including 8 cases of LLPCM, 5 LPL and 6 cases of RP were studied using dual IHC staining for Oct-2/CD138 and PAX5/CD138 and standard IHC staining for OBF-1. Co-expression of Oct2 and PAX5 in PC was measured as the percentage of Oct-2+ or PAX5+ cells per 200 CD138+cells.
Results: Median values and ranges for Oct2/CD138 and PAX5/CD138 staining in all categories are listed in the table below. NS-LLPCM demonstrated significantly lower Oct2 expression as compared to all categories (see Table). Oct-2 expression was also significantly lower in LLPCM as compared to PCM (p=0.002). As compared to PCM and RP, PAX5 expression was higher in LLPCM, including NS-LLPCM, (p=0.008, 0.001 respectively). Finally, OBF-1 expression, >85% in all cases, did not differ significantly among the categories.
|LLPCM||52.5 (7-95)||63 (15-85)|
|LPL||75 (32-95)||6 (5-22)|
|PCM||94.5 (74-99)||0 (0-82)|
|RP||78 (58-89)||0 (0-3)|