title: Nuclear overexpression of lymphoid-enhancer-binding factor 1 identifies chronic lymphocytic leukemia/small lymphocytic lymphoma in small B-cell lymphomas.
abstract: Lymphoid-enhancer-binding factor 1 (LEF1), coupling with β-catenin, functions as a key nuclear mediator of WNT/β-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 β-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 β-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/β-catenin signaling.
authors.affiliation: Division of Hematopathology, Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Bevan
authors.initials: B
authors.lastname: Tandon
authors.forename: Loann
authors.initials: L
authors.lastname: Peterson
authors.forename: Juehua
authors.initials: J
authors.lastname: Gao
authors.forename: Beverly
authors.initials: B
authors.lastname: Nelson
authors.forename: Shuo
authors.initials: S
authors.lastname: Ma
authors.forename: Steven
authors.initials: S
authors.lastname: Rosen
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002467:Cell Nucleus / Q000737:chemistry*; D002641:Chicago; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000473:pathology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000032:analysis*; D016393:Lymphoma, B-Cell / Q000737:chemistry* / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000737:chemistry / Q000473:pathology; D008224:Lymphoma, Follicular / Q000737:chemistry / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000737:chemistry / Q000473:pathology; D011237:Predictive Value of Tests; D015854:Up-Regulation; D051176:beta Catenin / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D051176:beta Catenin