[1438] Expression of Bone Marrow Stromal Antigen-2 (BST-2, CD317) in B-Cell Lymphomas

Elena Ivan, Mihaela Chiselite, Farah Keyoumarsi, Dafydd Thomas, Kojo SJ Elenitoba-Johnson, Megan S Lim. University of Michigan, Ann Arbor, MI; Spectrum Health, Grand Rapids, MI

Background: BST-2/CD317/HM1.24/tetherin is a type II transmembrane protein originally identified in terminally differentiated B cells of patients with multiple myeloma and later found to be expressed in many types of solid tumors. BST-2 is an interferon-inducible gene and a potent activator of NF-kB pathway, which is one of the main dysregulated pathways in the pathogenesis of B-cell lymphomas, in particular primary mediastinal B-cell lymphomas (PMBL) and classical Hodgkin lymphomas (CHL). Using mass spectrometry-based glycoproteomic profiling, we identified BST-2 as one of the proteins expressed at high levels in PMBL cell lines compared to CHL and diffuse large B-cell lymphoma (DLBCL) cell lines. The expression of BST-2 in lymphoma tissue has not been previously explored. Our objective was to evaluate the expression of BST-2 in a comprehensive panel of B-cell lymphomas to determine its diagnostic utility.
Design: Two antibodies were used to analyze the BST-2 expression in lymphoma cell lines derived from PMBL, CHL and DLBCL by Western blot and immunohistochemistry: the polyclonal B02P antibody (Abnova, Walnut, CA) and the monoclonal HM1.24 antibody (Chugai Pharmaceuticals, Tokyo, Japan). Tissue microarrays composed of PMBL, CHL, DLBCL, follicular lymphomas (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphomas (CLL/SLL) were used to evaluate the expression of BST-2. Cases with more than 15% positive neoplastic cells were scored as positive for BST-2. Z-test for independent proportions was used for statistical analysis.
Results: Western blot analysis demonstrated overexpression of a heavily glycosylated 25 kDa BST-2 in the PMBL cell lines compared to the CHL and DLBCL cell lines. BST-2 was expressed in 7/12 cases of PMBL and less frequently in the other types of B-cell lymphomas. Similar results were obtained with both antibodies, however the expression of BST-2 was more specific to PMBL using the monoclonal HM1.24 antibody.

Expression of BST-2 in B-cell lymphomas
PMBL7/12 (58.3%)
CHL7/56 (12.5%)
DLBCL12/56 (21.4%)
FL7/74 (9.4%)
CLL/SLL5/40 (12.5%)

Conclusions: BST-2 was expressed in a higher proportion of PMBL as compared to DLBCL (58.3% v. 21.4%, Z= 2.585), CHL (58.3% v. 12.5%, Z=3.563) and small B-cell lymphomas (58.3% v. 10.5%, Z=4.402). BST-2 may be useful in the workup of PMBL versus CHL and other types of B-cell lymphoma. Overexpression of BST-2 in PMBL suggests that BST-2 may play an important role in the pathogenesis of this disease. BST-2 may be a potential therapeutic target in B-cell neoplasms other than multiple myeloma.
Category: Hematopathology

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 199, Tuesday Afternoon


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