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.
|LEF1||GCB||ABC||Ki-67 (Mean+/-SD) (%)|
|Negative||30 (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|