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.