[1419] Expression of Notch Pathway Proteins in Hodgkin/Reed-Sternberg Cells of Classical Hodgkin Lymphoma

D Rakheja, P Kapur, W Chen. UT Southwestern Medical Center, Dallas, TX

Background: The Notch family of transmembrane receptors mediates an evolutionarily conserved signal transduction pathway involved in cell proliferation and differentiation during fetal development. Canonical Notch signaling is activated when the binding of Notch receptors (Notch1–4) with their ligands (Delta-like1, 3, and 4, and Jagged1 and 2) triggers proteolytic cleavages resulting in the release of the respective Notch intracellular domain (NICD). The NICD translocates to the nucleus, where it is a part of a transcriptional activation complex that induces transcription of genes involved in cell proliferation. While the aberrant activation of Notch1 pathway has been implicated in pathogenesis of Classical Hodgkin lymphoma (CHL), the role of other Notch proteins has not yet been characterized.
Design: Immunohistochemistry (IHC) was performed on tissue microarray constructs consisting of 44 cases of pediatric CHL (age 4-19 years, 23 females, 21 males). The sections were stained by standard immunoperoxidase techniques for Notch1 (Chemicon), Notch2 (Abcam), Notch3 (Abcam), Notch4 (Santa Cruz), and the Notch ligand Jagged1 (Abcam). The results in Hodgkin/Reed-Sternberg cells were recorded as the average of duplicate staining and categorized as either weak (weak staining in a few cells) or strong (strong staining in most cells).
Results: The IHC results are summarized in the table. Notch1 and Notch3 expressions were strong in 98% of the cases. The staining pattern was nuclear/cytoplasmic or cytoplasmic for Notch1, and nuclear/cytoplasmic/membranous or cytoplasmic/membranous or membranous for Notch3. Overall, nuclear staining for Notch1 was seen in 65% of cases and for Notch3 in 52% of cases. IHC expressions for Notch2, Notch4, and Jagged1 were not significant.

IHC Results
weak (% of cases)strong (% of cases)
Notch1298 (nuclear staining in 65%)
Notch2937
Notch3298 (nuclear staining in 52%)
Notch4982
Jagged1982



Conclusions: Our results confirm strong expression of Notch1 in CHL. Further, we demonstrate, for the first time in CHL, strong expression of Notch3 with variable nuclear immunoreactivity. These results suggest that Notch signaling pathway may play an important role in the pathogenesis of CHL and provide new targets for CHL therapy.
Category: Hematopathology

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 200, Wednesday Morning

 

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