Expression of Grb2 distinguishes classical Hodgkin lymphomas from primary mediastinal B-cell lymphomas and other diffuse large B-cell lymphomas.
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.
Miles
Rodney R
RR
Department of Pathology, University of Utah, Salt Lake City, UT 84112-0565, USA.
Mankey
Cohra C
CC
Seiler
Charlie E
CE
Smith
Lauren B
LB
Teruya-Feldstein
Julie
J
Hsi
Eric D
ED
Elenitoba-Johnson
Kojo S J
KS
Lim
Megan S
MS
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
D014408:Biomarkers, Tumor; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human