[1326] Expression of Phosphoprotein Associated with Glycosphingolipid Enriched Microdomains 1 Protein (PAG1) in B and T-Cell Lymphomas

Megan A Alderman, Delphine Rolland, Farah Keyoumarsi, Dafydd Thomas, Kojo Elenitoba-Johnson, Megan Lim, Elena Ivan. University of Michigan Health System, Ann Arbor, MI

Background: Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) is a transmembrane adaptor with a negative regulatory role in lymphocyte activation and signaling. Using mass spectrometry-based phosphoproteomics, we identified PAG1 as an abundantly phosphorylated protein in germinal center derived cell lines. PAG1 expression has been studied in small cohorts of B-cell but not T-cell lymphomas. Our goal was to evaluate PAG1 expression in a comprehensive panel of B-cell as well as T-cell lymphomas to determine its diagnostic utility.
Design: Tissue microarrays composed of B and T-cell lymphomas were constructed from material at the University of Michigan. Diagnoses included mantle cell lymphoma (MCL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), diffuse large B-cell lymphoma both germinal center B-cell-like (GCB) and non-germinal center B-cell-like (non-GCB), Burkitt lymphoma (BL), classical Hodgkin lymphoma (CHL), peripheral T-cell lymphoma not otherwise specified (PTCL, NOS) and anaplastic large cell lymphoma (ALCL). Immunohistochemistry was performed with monoclonal antibody anti-PAG1. Cases with more than 15% positive neoplastic cells were scored as positive for PAG1. Reactive tonsil was used as a control.
Results: PAG1 was expressed more frequently in germinal center derived B-cell lymphomas; 81% of GC-DLBCL, 67% of FL, and 90% of BL cases compared to non-GC DLBCL (49%) and other B-cell lymphomas. In the T-cell lymphoma group, PAG1 was expressed in 86% of ALCL and in 64% of PTCL NOS.

DLBCL, GCB69/85 (81%)
DLBCL, nonGCB115/237 (49%)
FL124/185 (67%)
BL18/20 (90%)
MCL2/43 (5%)
CLL/SLL12/86 (14%)
CHL10/133 (8%)
PTCL, NOS59/92 (64%)
ALCL37/43 (86%)

Conclusions: Our study shows PAG1 is expressed in a higher proportion of GC derived B-cell lymphomas (BL and FL) as compared with non GC B-cell lymphomas (MCL and CLL/SLL) (69% v. 11%, p<0.0001). Among DLBCLs, PAG1 expression was observed more often in GC subtype compared to non-GC subtype (81% v. 48%, p<0.001). PAG1 was also expressed in T-cell lymphomas, more often in ALCL than PTCL, NOS (86% v. 64%, p<0.01). PAG1 was expressed strongly in reactive germinal centers. Interestingly, most CHL neoplastic cells did not express PAG1. Given the negative regulatory role of PAG1 in B-cell receptor signaling, the absence of its expression in CHL may reflect the aberrant B-cell receptor signaling in these tumors and warrant further studies to evaluate the biologic significance of PAG1 in the pathogenesis of CHL.
Category: Hematopathology

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 166, Tuesday Morning


Close Window