title: Loss of expression of the WNT/beta-catenin-signaling pathway transcription factors lymphoid enhancer factor-1 (LEF-1) and T cell factor-1 (TCF-1) in a subset of peripheral T cell lymphomas.
abstract: T cell factor-1 (TCF-1) and lymphoid enhancer factor-1 (LEF-1), members of the TCF/LEF family of transcription factors, play a significant role in T cell development and are expressed in thymocytes and peripheral CD3+ T cells. Previously, precursor T lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LyL) was found to express TCF-1, and we find that 9 of 10 cases of T-ALL/LyL express LEF-1 as well as TCF-1, exhibiting uniform nuclear immunostaining for both transcription factors. In addition, a significant subset of cases of peripheral T cell lymphoma (PTCL), 39 of 81 cases (48%), are immunoreactive for LEF-1 and/or TCF-1, with 36 of 38 cases immunoreactive for both, indicating that these transcription factors are coordinately expressed in PTCL. The vast majority of LEF-1+ and/or TCF-1+ PTCL (34 of 39 or 87%) exhibit a composite Th1 T-cell-like immunophenotype, based on expression of Th1 T cell-associated, but not Th2 T cell-associated, chemokine receptors and activation markers. Of the Th1-like PTCL studied, 33 of 42 (79%) were immunoreactive for LEF-1 and 32 of 42 (76%) were immunoreactive for TCF-1, including most cases of angioimmunoblastic lymphoma and all cases of lymphoepithelioid lymphoma. Surprisingly, none of the 21 cases of Th2-like PTCL studied, all cases of anaplastic large cell lymphoma, were immunoreactive for LEF-1 or TCF-1 (P < 0.0001), suggesting that LEF-1 and TCF-1 transcription factor expression may be lost in Th2 T cells or Th2-like PTCL. LEF-1 and TCF-1 immunostaining can serve to identify specific subtypes of PTCL, and lends support to a bipartite model of PTCL development, based on expression of activation markers.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. ddorfman@partners.org
authors.forename: David M
authors.initials: DM
authors.lastname: Dorfman
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Greisman
authors.forename: Aliakbar
authors.initials: A
authors.lastname: Shahsafaei
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: D015415:Biomarkers; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D011505:Protein-Tyrosine Kinases