Expression of C-Rel in High-Grade B-Cell Lymphomas with MYC Rearrangement: Impact on Survival
A Gonzalez-Longoria, R Kolhe, P Ramalingam, LJ Medeiros, CE Bueso-Ramos. Medical College of Georgia, Augusta, GA; MD Anderson Cancer Center, Houston, TX
Background: Burkitt lymphoma (BL) and B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU), as defined by the WHO classification, are aggressive B-cell lymphomas that show a high growth fraction and level of apoptosis. Distinction of BL and BCLU can be difficult using traditional histologic and immunophenotypic criteria and MYC rearrangement occurs in both entities. The nuclear factor-kB (NF-kB) signaling pathway plays an important role regulating survival of normal and malignant B-cells by controlling the expression of multiple cell death regulatory pathways. The c-Rel transcription factor is a member of the Rel/NF-kB family, which also includes p65, RelB, p50, and p52. C-Rel has been shown to be capable of transforming cells in culture. The recent development of NF-kB inhibitors may make this pathway a potential therapeutic target for lymphoma. The goal of this study was to assess c-Rel expression in BL and BCLU, and correlate its relationship with survival.
Design: 29 cases of high-grade B-cell lymphoma with MYC rearrangement arising in adults who had available clinical follow (median, 13 months; range, 1-47 months) were selected for this study. Using the 2008 WHO classification criteria, 19 cases were classified as BL and 10 were classified as BCLU. All cases were assessed for B-cell and T-cell antigens as part of their routine workup. All neoplasms were B-cell, CD10/Bcl6 +, and Ki-67 high (>95%). For this study all cases were assessed for c-Rel using immunohistochemistry. Nuclear expression of c-Rel in > 5% of tumor cells was defined as a positive result.
Results: The lymphomas were classified as 19 BL and 10 BCLU. Nuclear expression of c-Rel was observed in a total of 18 (62%) cases, including 10 (53%) BL and 8 (80%) BCLU. In the BL group, c-Rel nuclear expression appears to be associated with increased mortality (5/10 c-Rel+ versus 1/9 c-Rel- died; p-0.14 Fisher's exact test).
|c-Rel expression||Died of disease|
|+ (>5%)||- (0-5%)||c-Rel +||c-Rel -|
|BL (19/29)||10||9||5/10 (50%)||1/9 (11%)|
|BCLU (10/29)||8||2||4/8 (50%)||1/2 (50%)|
|Total||18||11||9/18 (50%)||2/11 (18%)|