Lymphoid enhancer-binding factor 1 (LEF1) is a mediator of the Wnt/β-catenin pathway, which regulates cell proliferation and survival, and shows nuclear expression by immunohistochemistry. It is normally expressed in T cells and pre-B cells. Mature B cells do not express LEF1.
It is characteristically expressed in >95% of cases of CLL/SLL (including CD5 negative cases), and is not (thought) to be expressed in mantle cell lymphoma (MCL). A subset of cases of follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) with LEF-1 expression have been described. In current data sets, LEF1 expression has not been identified in other low grade lymphomas, such as marginal zone lymphoma (MZL) and grade 1-2 follicular lymphoma (FL).
In a study by O’Malley et al., 2 of 23 cases of MCL were found to express (strong uniform expression) LEF1. When combining with other institutional data there is an approximate expression rate of 4% (n=98). This reinforces the importance of using an antibody panel when evaluating cases.
Higher LEF1-mRNA expression is associated with worse prognosis and disease progression in the setting of CLL.
LEF1 expression (Tandon et al.)
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CLL/SLL
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100% (n=92)
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|
MCL
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0% (n=53)
|
|
– Classical
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0/47
|
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– Small Cell Var.
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0/2
|
|
– Pleo./Blastoid
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0/4
|
|
MZL
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0% (n=31)
|
|
– Nodal
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0/15
|
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– Splenic
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0/3
|
|
– MALT
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0/13
|
|
FL
|
|
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– Low grade
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0/31
|
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– Grade 3
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6/12 (5-15% of cells)
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|
DLBCL
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38% (n=71)
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Photomicrographs
References
O’Malley DP, Lee JP, Bellizzi AM. Expression of LEF1 in mantle cell lymphoma. Annals of Diagnostic Pathology. 2017;26: 57–59. doi:10.1016/j.anndiagpath.2016.09.016
Tandon B, Peterson L, Gao J, Nelson B, Ma S, Rosen S, et al. Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell lymphomas. Mod Pathol. 2011;24: 1433–1443. doi:10.1038/modpathol.2011.103
Gutierrez A, Arendt BK, Tschumper RC, Kay NE, Zent CS, Jelinek DF. Differentiation of chronic lymphocytic leukemia B cells into immunoglobulin secreting cells decreases LEF-1 expression. PLoS ONE. 2011;6: e26056. doi:10.1371/journal.pone.0026056
Zhang XM, Aguilera N. New immunohistochemistry for B-cell lymphoma and Hodgkin lymphoma. Arch Pathol Lab Med. 2014;138: 1666–1672. doi:10.5858/arpa.2014-0058-RA
Wu W, Zhu H, Fu Y, Shen W, Miao K, Hong M, et al. High LEF1 expression predicts adverse prognosis in chronic lymphocytic leukemia and may be targeted by ethacrynic acid. Oncotarget. 2016;7: 21631–21643. doi:10.18632/oncotarget.7795