[1396] Expression of B7-H3 (CD276) an Immunoregulatory Cell Surface Molecule in Non-Hodgkin Lymphomas Identified by Mass Spectrometry.

Elizabeth A Wey, Julie Laliberta, Carla McNeil, Venkatesha Basrur, Farah Keyoumarsi, Dafydd Thomas, Cheolwon Suh, Jooryung Huh, Kojo Elenitoba-Johnson, Megan S Lim. University of Michigan, Ann Arbor; Asan Medical Center, Seoul, Korea

Background: B7-H3 is a member of the B7/CD28 superfamily of immunoregulatory molecules. Inhibition of T-cell mediated antitumor immunity by B7-H3 is involved in the immune evasion activity of cancer. Its expression is associated with increased risk of recurrence and poor survival in prostate and renal cancers. Using mass spectrometry-based glycoproteomic profiling, we identified B7-H3 as a selectively expressed protein in anaplastic large cell lymphoma (ALCL)-derived cell lines. We hypothesized that B7-H3 is expressed in distinct categories of human lymphoma.
Design: Lymphoma derived cell lines from B and T-cell lineage (n=10) were used for western blot analyses. Immunohistochemistry was performed on lymphoma tissue microarrays composed of 828 lymphomas using anti-human B7-H3 antibody and were evaluated using a combination of staining intensity and percentage of immunoreactive neoplastic cells.
Results: Western blot analysis demonstrated selective expression of B7-H3 in 3/5 ALCL-derived cell lines. B-cell lymphoma-derived cell lines did not express B7-H3. In reactive lymph nodes, B7-H3 was primarily expressed in the germinal center B-cells and in the follicular dendritic cells. B7-H3 was expressed in neoplastic cells of 6/32 (18.8%) ALCL, independent of ALK status and in 11/92 (12%) of other PTCL. Only rare cases (21/704) of other lymphoma subtypes expressed B7-H3.

B7-H3/CD276 Expression in Lymphoma*
Follicular Lymphoma1.1% (2/183)
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma1.2% (1/82)
Mantle Cell Lymphoma0% (0/26)
Diffuse Large Cell Lymphoma4.1% (10/245)
Hodgkin Lymphoma5.3% (8/150)
Nodular Lymphocyte Predominant Hodgkin Lymphoma0% (0/18)
Anaplastic Large Cell Lymphoma18.8% (6/32)
Peripheral T Cell Lymphoma12% (11/92)
*Percentage of neoplastic cells with moderate to strong staining in 25% or more cells


Conclusions: B7-H3 was expressed in a higher proportion of the T-cell lymphomas as compared to small B-cell lymphomas (13.7% v. 2.4%, Z=5.195). In addition, when comparing aggressive lymphomas (T-cell and DLBCL) to low grade B-cell lymphomas, expression of B7-H3 is higher in aggressive lymphomas (7.3% v. 1.0%, Z=3.664). Higher levels of B7-H3 expression suggest a role for B7-H3-mediated inhibition in the pathogenesis of aggressive lymphomas.
Category: Hematopathology

Tuesday, March 1, 2011 1:00 PM

Poster Session IV # 159, Tuesday Afternoon

 

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