title: Expression of Grb2 distinguishes classical Hodgkin lymphomas from primary mediastinal B-cell lymphomas and other diffuse large B-cell lymphomas.
abstract: Growth factor receptor-bound protein 2 is an adaptor molecule that mediates B-cell receptor (BCR) signaling pathways, but the expression of growth factor receptor-bound protein 2 in lymphoma tissues has not been reported. We sought to characterize growth factor receptor-bound protein 2 protein expression in reactive tonsillar tissues and lymphoma tissues obtained from diagnostic biopsies of classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and 20 low-grade B-cell lymphomas. Growth factor receptor-bound protein 2 expression was assessed in tissues by immunohistochemistry and in lymphoma cell lines by immunoblotting. In reactive lymphoid tissues, growth factor receptor-bound protein 2 was expressed in the cytoplasm of B-cells and histiocytes but not T-cells. Strong, cytoplasmic growth factor receptor-bound protein 2 expression was seen in the neoplastic cells of follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, splenic marginal zone lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma, and nodular lymphocyte predominant Hodgkin lymphoma. In contrast, only 10% of the classical Hodgkin lymphomas showed growth factor receptor-bound protein 2 expression in the neoplastic cells. Growth factor receptor-bound protein 2 protein expression was detected by Western blotting in all lymphoma cell lines tested with higher levels in primary mediastinal large B-cell lymphoma compared with classical Hodgkin lymphoma cell lines. These findings support a role for growth factor receptor-bound protein 2 in the diagnostically challenging workup of classical Hodgkin lymphoma versus primary mediastinal large B-cell lymphoma and warrant further studies to evaluate the biologic significance of growth factor receptor-bound protein 2 in the pathogenesis of classical Hodgkin lymphoma.
authors.affiliation: Department of Pathology, University of Utah, Salt Lake City, UT 84112-0565, USA.
authors.forename: Rodney R
authors.initials: RR
authors.lastname: Miles
authors.forename: Cohra C
authors.initials: CC
authors.lastname: Mankey
authors.forename: Charlie E
authors.initials: CE
authors.lastname: Seiler
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Smith
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Kojo S J
authors.initials: KS
authors.lastname: Elenitoba-Johnson
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lim
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D003937:Diagnosis, Differential; D051380:GRB2 Adaptor Protein / Q000096:biosynthesis*; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000378:metabolism; D008479:Mediastinal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human