Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies CLL/SLL in small B-cell lymphomas.

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BlankNuclear overexpression of lymphoid-enhancer-binding factor 1 identifies

chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell

lymphomas.

B Tandon, L , J Gao, B , S Ma, S Rosen, and YH Chen

Mod Pathol, June 17, 2011; .

Division of Hematopathology, Department of Pathology, Northwestern University

Feinberg School of Medicine, Chicago, IL, USA.

Lymphoid-enhancer-binding factor 1 (LEF1), coupling with ?-catenin, functions as

a key nuclear mediator of WNT/?-catenin signaling, which regulates cell

proliferation and survival. LEF1 has an important role in lymphopoiesis, and is

normally expressed in T and pro-B cells but not mature B cells. However, gene

expression profiling demonstrates overexpression of LEF1 in chronic lymphocytic

leukemia, and knockdown of LEF1 decreases the survival of the leukemic cells. So

far, the data on LEF1 expression in B-cell lymphomas are limited. This study

represents the first attempt to assess LEF1 by immunohistochemistry in a large

series (290 cases) of B-cell lymphomas. Strong nuclear staining of LEF1 was

observed in virtually all neoplastic cells in 92 of 92 (100%) chronic

lymphocytic leukemia/small lymphocytic lymphomas including two CD5- cases, with

strongest staining in cells with Richter's transformation. LEF1 also highlighted

the morphologically inconspicuous small lymphocytic lymphoma component in three

composite lymphomas. All 53 mantle cell lymphomas, 31 low-grade follicular

lymphomas and 31 marginal zone lymphomas, including 3 CD5+ cases, were negative.

In 12 grade 3 follicular lymphomas, LEF1 was positive in a small subset (5-15%)

of cells. Diffuse large B-cell lymphoma, however, demonstrated significant

variability in LEF1 expression with overall positivity in 27 of 71 (38%) cases.

Our results demonstrate that nuclear overexpression of LEF1 is highly associated

with chronic lymphocytic leukemia/small lymphocytic lymphoma, and may serve as a

convenient marker for differential diagnosis of small B-cell lymphomas. The

expression of ?-catenin, the coactivator of LEF1 in WNT signaling, was examined

in 50 chronic lymphocytic leukemia/small lymphocytic lymphomas, of which 44

(88%) showed negative nuclear staining. The findings of universal nuclear

overexpression of LEF1 but lack of nuclear ?-catenin in the majority of chronic

lymphocytic leukemia/small lymphocytic lymphoma suggest that the pro-survival

function of LEF1 in this disease may be independent of WNT/?-catenin

signaling.Modern Pathology advance online publication, 17 June 2011;

doi:10.1038/modpathol.2011.103.

PMID: 21685909