Expression of Grb2 distinguishes classical Hodgkin lymphomas from primary mediastinal B-cell lymphomas and other diffuse large B-cell lymphomas

Miles, Rodney R.; Mankey, Cohra C.; Seiler, Charlie E.; Smith, Lauren B.; Teruya-Feldstein, Julie; Hsi, Eric D.; Elenitoba-Johnson, Kojo S.J.; Lim, Megan S.

doi:10.1016/j.humpath.2009.05.009

« Previous Next »Human Pathology
Volume 40, Issue 12 , Pages 1731-1737, December 2009

Expression of Grb2 distinguishes classical Hodgkin lymphomas from primary mediastinal B-cell lymphomas and other diffuse large B-cell lymphomas

Rodney R. Miles, MD, PhD
- Department of Pathology, University of Utah, Salt Lake City, UT 84112-0565, USA
Cohra C. Mankey, MD
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA
Charlie E. Seiler III, MS
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA
Lauren B. Smith, MD
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA
Julie Teruya-Feldstein, MD
- Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
Eric D. Hsi, MD
- Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Kojo S.J. Elenitoba-Johnson, MD
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA
Megan S. Lim, MD, PhD
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0602, USA
- Corresponding author.

Received 1 April 2009; received in revised form 20 May 2009; accepted 22 May 2009. published online 28 August 2009.

Summary

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.

Keywords: Grb2 adaptor protein, Primary mediastinal large B-cell lymphoma, Hodgkin lymphoma, Diffuse large B-cell lymphoma, Lymphoma, B-cell