[1407] Evaluation of Nuclear Overexpression of Lymphoid-Enhancer-Binding Factor 1 (LEF1) in Diffuse Large B-Cell Lymphoma and Correlation with Hans Classification and Proliferation Index

Juehua Gao, Josette William, Yi-Hua Chen. Northwestern University Feinberg School of Medicine, Chicago, IL

Background: LEF1 is a key nuclear mediator of WNT/beta-catenin signaling which regulates cell proliferation and survival. Our previous study demonstrated nuclear overexpression of LEF1 is highly specific for small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL) among small B-cell lymphomas, and is also present in a subset of diffuse large B-cell lymphoma (DLBCL). In this study, we evaluated LEF1 expression in DLBCL and correlated with currently accepted prognostic indicators, Hans classification (GCB vs ABC) and proliferation index.
Design: Cases diagnosed as DLBCL between 01/2002 and 11/2010 were retrieved from the Department of Pathology at the Northwestern Memorial Hospital. DLBCLs transformed from low-grade B cell lymphoma were excluded from the study. Expression of LEF1, CD10, BCL-6, MUM1 and Ki-67 were examined by immunohistochemical (IHC) staining on paraffin-embedded tissue sections. The percentage of positive staining in the lymphoma cells was recorded. LEF1 positivity was defined as nuclear staining in >10% of lymphoma cells.
Results: Based on the IHC results, 42 of 75 (56%) DLBCLs were GCB and 33 (44%) were ABC subtype according to the Hans classification. IHC for LEF1 demonstrated highly variable staining in the lymphoma cells from negative to positive in over 80% of cells. Fourteen of 33 (42%) cases of ABC subtype and 12 of 42 (29%) GCB subtype were positive for LEF1. Eleven cases demonstrated high nuclear LEF1 expression in >60% of the lymphoma cells, among which 7 were GCB and 4 were ABC subtype. Statistical analysis showed that positive LEF1 staining was not significantly correlated with GCB/ABC status (p=0.21, Chi square test). However, increased percentage of LEF1 expression demonstrated a tendency of association with higher proliferation index, though it did not reach statistical significance.

Table 1. Nuclear expression of LEF1 in DLBCLs and correlation with Hans classification and proliferation index (n=75)
LEF1GCBABCKi-67 (Mean+/-SD) (%)
Negative30 (40%)19 (25.3%)62+/-22
11-30%2 (2.7%)4 (5.3%)69+/-16
31-60%3 (4%)6 (8%)75+/-24
>60%7 (9.3%)4 (5.3%)81+/-23

Conclusions: Our study showed that nuclear overexpression of LEF1 is present in 35% of DLBCL, which suggests that WNT/beta-catenin signaling may be involved in the development and/or progression of a subset of DLBCL. Positive nuclear staining of LEF1, however, is not correlated with GCB/ABC status, but shows a tendency of association with higher proliferation index.
Category: Hematopathology

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 184, Tuesday Afternoon


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