CD30 Expression Correlates with Increased Levels of the Anti-Apoptotic Protein BAG-3 in T-Cell Lymphomas
L Jiang, C Cocklin, D Menke, KA Rizzo. Indiana University, Indianapolis, IN; Mayo Clinic, Jacksonville, FL
Background: T-cell lymphomas have an overall poor prognosis and resistance to therapy. The BAG-3 protein functions in chemotherapeutic resistance and cellular survival through the ubiquitin-proteasome system which is targeted by proteasome and HSP90 inhibitors. The anti-apoptotic role of BAG-3 has been demonstrated in carcinoma cells; however its role in T-cell lymphomas has not been investigated. We undertook a study to analyze the protein expression levels of BAG-3 in T-cell lymphomas.
Design: 51 cases were evaluated, including 8 benign lymphoid cases and 43 systemic and primary cutaneous T-cell lymphomas. Anti-BAG-3 immunohistochemical (IHC) stain was evaluated on 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. A subset of systemic T-cell lymphomas showed increased BAG-3 expression. Comparison between BAG-3 expression profile and the IHC profile of the T-cell lymphomas demonstrated a correlation with increased BAG-3 expression and co-expression of CD30. 20 of 22 cases of CD30 positive systemic T-cell lymphomas had a BAG-3 quantitative score of 2 (average quantitative score of 1.9). These cases showed a statistically significant increase in the expression of BAG-3 when compared to systemic T-cell lymphomas negative for CD30 (average quantitative score of 0.6; p < 0.05 x 10^8). Correlation between BAG-3 and CD30 expression was not seen in primary cutaneous T-cell lymphomas (average quantitative score of 1.6). Primary cutaneous T-cell lymphomas quantitatively showed a significant increase in BAG-3 staining when compared to CD30 negative systemic T-cell lymphomas (p < 0.04 x 10^4) but showed no statistical difference when compared to CD30 positive systemic T-cell lymphomas (p = 0.11). There was no difference in the quality of BAG-3 staining between the CD30 positive systemic T-cell lymphomas and the primary cutaneous T-cell lymphomas (p = 0.16).
Conclusions: Increased BAG-3 levels showed a specific correlation with CD30 expression in systemic T-cell lymphomas. However, cutaneous T-cell lymphomas demonstrated increased BAG-3 levels irrespective of CD30 expression. The differential protein expression profile of BAG-3 may indicate a specific role of this anti-apoptotic protein and the ubiquitin-proteasome system in T-cell lymphomas and may help guide future targeted therapy.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 198, Tuesday Morning