Overexpression of Lymphoid Enhancer Binding Factor 1 (LEF-1) Is Highly Associated with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) in Small B-Cell Lymphomas.
Bevan Tandon, Juehua Gao, LoAnn Peterson, Yi-Hua Chen. Northwestern University Feinberg School of Medicine, Chicago, IL
Background: Recent studies have shown that the Wnt/β-catenin signaling pathway may contribute to the defects in apoptosis in CLL/SLL. LEF-1 is a key molecule in this pathway. It binds to β-catenin in the nucleus to form a complex and subsequently induce the transcription of target genes involving cellular proliferation and apoptosis. Our study evaluated the nuclear expression of LEF-1 by immunohistochemistry (IHC) in a large series of CLL/SLL and various other B-cell lymphomas.
Design: IHC for LEF-1 was performed on paraffin-embedded sections of 259 B-cell lymphomas including 76 CLL/SLLs, 52 mantle cell lymphomas (MCL), 31 follicular lymphomas (FL), 20 marginal zone lymphomas (MZL), and 80 diffuse large B-cell lymphomas (DLBCL). Normal lymph node was used for control.
Results: In a normal lymph node, nuclear staining of LEF-1 was seen only in T cells; the B cells were negative. However, strong nuclear staining of LEF-1 was observed in virtually 100% of neoplastic cells in all 76 CLL/SLLs. In 7 additional CLL/SLLs with foci of Richter's transformation, LEF-1 staining in the transformed large cells was stronger. All other small B-cell lymphomas (52 MCLs, 20 MZLs, 31 FLs) were negative, including 2 small cell variant MCLs morphologically mimicking CLL/SLL. In one composite lymphoma (SLL and MCL), LEF-1 staining was restricted to the cyclin D1-negative SLL component. Thirty nine of 80 (48%) DLBCLs were positive for LEF-1, but demonstrated variable staining intensity in a subset of cells.
Conclusions: (1). To date, the diagnosis of CLL/SLL has been based on morphology and immunophenotype with no characteristic IHC marker available. Our study show that overexpression of LEF-1 is highly associated with CLL/SLL among small B-cell lymphomas, indicating it may serve as an IHC marker for CLL/SLL, especially in cases where immunophenotypic data are not available. (2). Overexpression of LEF-1 in all CLL/SLLs but not in other small B-cell lymphomas strongly suggests that Wnt/β-catenin signaling may play an important role in the pathogenesis of the disease. (3). LEF-1 may be a potential therapeautic target for patients with CLL/SLL and Richter's transformation.
Monday, February 28, 2011 9:00 AM
Platform Session: Section B, Monday Morning