Increased Expression of the Anti-Apoptotic Protein BAG-3 in High-Grade B Cell Lymphomas and Plasma Cell Myelomas
C Zhang, KA Rizzo. Indiana University, Indianapolis, IN
Background: BAG-3 is an anti-apoptotic protein which functions in the ubiquitin-proteasome system which is targeted by proteasome and HSP90 inhibitor therapies. In epithelial cell lines, increased levels of BAG-3 are associated with chemotherapeutic resistance and cellular survival. Proteasome inhibitors, a common therapy utilized in plasma cell myeloma, have also been shown to cause an increase in BAG-3 levels in carcinoma and sarcoma cell lines. Thus we undertook a study to analyze the protein expression levels of BAG-3 in benign lymphoid cells, low-grade B cell lymphomas, high-grade B cell lymphomas and plasma cell neoplasms.
Design: Thirty six cases were evaluated and included 6 high-grade B cell lymphomas; 11 low-grade B cell lymphomas; 11 plasma cell neoplasms (10 plasma cell myelomas, 1 plasmablastic lymphoma) and 8 benign lymphoid cases. Anti-BAG-3 immunohistochemical (IHC) staining was performed and evaluated on the basis of quantity of cells positive: 0 = negative, 1 = <25% positive, 2 = >25% positive; and quality of staining intensity: 0 = negative, 1 = weak/moderate, 2 = strong.
Results: All benign lymphoid cases were negative for BAG-3 staining. Increased BAG-3 IHC staining was seen in the high-grade lymphomas (average quantitative score of 1.17) compared with low grade B cell lymphomas (average quantitative score of 0.55) and showed a statistical difference, p = 0.03. All plasma cell neoplasms had a BAG-3 quantitative score of 2 and showed a significant increased expression level when compared with the high grade B cell lymphomas (p < 0.05 x 10^4). In the B cell lymphomas, quantitative levels of BAG-3 did not correlate with expression levels of one of its binding partners, bcl-2. The differences of staining quality among the plasma cell neoplasms did not correlate with immunoglobulin heavy or light chain subtype or primary versus persistent disease presentation. The differences of staining intensity among the low grade and high grade lymphomas did not correlate with a specific lymphoma subtype.
Conclusions: Increased BAG-3 expression was seen in plasma cell neoplasms and to a lesser extent in high grade B cell lymphomas. BAG-3 expression was not significantly seen in low-grade B cell lymphomas including those with plasmacytic differentiation. The differential protein expression profile of BAG-3 further indicates a specific role for this anti-apoptotic protein and the ubiquitin-proteasome system in plasma cell neoplasms and a potential role in high grade B cell lymphomas.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 189, Wednesday Morning