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The Reed-Sternberg Cell: Molecular Characterization by Proteomic Analysis with Therapeutic Implications

Address correspondence to Robert E. Brown, M.D., Division of Laboratory Medicine, Geisinger Medical Center, Danville, PA 17822-0131, USA; tel 570 271 6332; fax 570 271 6105; e-mail rebrown{at}geisinger.edu.

Objective: To characterize Reed-Sternberg (R-S) cells by proteomic analysis in order to gain insight into the molecular pathways that control their growth and thereby to discern potential molecular interventions in Hodgkin’s disease. Methods: Ten cases of the nodular sclerosing (NS) subtype and 4 cases of the lymphocyte-predominant (LP) subtype were studied. Immunohistochemical procedures were performed to detect the following antigens: CD20, CD30, c-kit, platelet-derived growth factor receptor (PDGFR)-, cathepsin D, angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor, phosphorylated c-Jun N-terminal kinase (p-JNK), c-Jun, Ki-67, the latency-associated peptide (LAP) of transforming growth factor-beta 1 (TGF-ß1), and the TGF-ß receptor (TGF-ßRII). Immunoreactivities were scored from 0 to 3+ positivity using bright-field microscopy. Results: The tyrosine kinase signal transducer, PDGFR-, the AT1 receptor transactivator, the p-JNK downstream effector, Ki-67, and proapoptotic TGF-ß1 (LAP) were detected in R-S cells of the NS and LP subtypes; companion dendritic cells expressed cathepsin D and ACE. Intranuclear c-Jun was present in the NS subtype and stronger immunoreactivity for TGF-ßRII was evident in the LP subtype. Conclusion: These data corroborate observations in the literature, characterizing R-S cells as possessing molecular pathways that incorporate PDGFR- signaling and angiotensin transactivation with a potential for growth inhibition through activation of TGF-ß1 and upregulation of its receptor. Specific therapies to target R-S cells in Hodgkin’s disease might include STI571, an AT1 receptor inhibitor, and retinoids.

Keywords: Reed-Sternberg cell, proteomics, immunohistochemistry, Hodgkin’s disease, molecular signaling pathways

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