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: Rodney R Miles, Cohra C Mankey, Charlie E Seiler 3rd, Lauren B Smith, Julie Teruya-Feldstein, Eric D Hsi, Kojo S J Elenitoba-Johnson, Megan S Lim
• Journal: Human pathology (Hum Pathol) Vol. 40 Issue 12 Pg. 1731-7 (Dec 2009) ISSN: 1532-8392 [Electronic] United States
• PMID: 19716163 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• GRB2 Adaptor Protein
• GRB2 protein, human

Topics

• Biomarkers, Tumor (analysis)
• Blotting, Western
• Diagnosis, Differential
• GRB2 Adaptor Protein (biosynthesis)
• Hodgkin Disease (diagnosis, metabolism)
• Humans
• Immunohistochemistry
• Lymphoma, Large B-Cell, Diffuse (diagnosis, metabolism)
• Mediastinal Neoplasms (diagnosis, metabolism)
• Tissue Array Analysis