Differential Expression of Aurora-A Kinase in Primary Mediastinal (Thymic) Large B-Cell Lymphoma and Classical Hodgkin Lymphoma Involving the Mediastinum
RK Shamanna, ME Salama, N Lehman, KV Inamdar. Henry Ford Hospital, Detroit, MI; University of Utah, Salt Lake City, UT
Background: Mediastinal (thymic) large B-cell lymphoma (MLBCL) shares many morphologic and phenotypic similarities with classical Hodgkin lymphoma (CHL) that specifically involves the mediastinum. Both contain large neoplastic cells with lacunar cytomorphology in a fibrotic stroma. Immunophenotypically, the distinction can sometimes be challenging, especially in smaller biopsies. Recent gene expression profiling studies reveal similarities in gene signatures between the two entities. Distinction between MLBCL and CHL is critical from therapeutic standpoint. Aurora A kinase (AA), a cell-cycle regulating Ser/Thr kinase has been implicated in the pathogenesis of a variety of B-cell non-Hodgkin's lymphomas but its role in the pathogenesis of MLBCL has not been explored to date. We thus assessed its expression in MLBCL and explored its utility in distinction from CHL.
Design: We assessed 15 cases of MLBCL and 5 CHL involving the mediastinum for AA expression by immunohistochemistry. A mouse monoclonal AA-antibody was used (Bethyl Labs, USA). Each case was assessed for cytoplasmic and/or nuclear expression of AA and was semi-quantitatively graded for staining intensity (0-3+). Fisher's exact test was used for statistical analysis.
Results: AA was detected in 14/15 (93.3%) MLBCL and 5/5 (100%) CHL. Nuclear expression of AA was seen in 13/15 (87%) MLBCL whereas cytoplasmic expression was seen in 1 case. AA was not expressed in 1 case. In contrast to MLBCL, AA was expressed in the nucleus as well as in the cytoplasm of Hodgkin and Reed-Sternberg cells in all cases of CHL (100%) (p<0.001). When assessed for staining intensity, 1+ staining was noted in tumor cells of 10/15 (67%) of MLBCL where as 2+ and 3+ staining intensity was observed in 2 (13.3%) cases for each category. In contrast to MLBCL, tumor cells in all CHL cases (5/5, 100%) showed a 3+ staining intensity (p<0.001).
Conclusions: The differential expression in MLBCL and CHL implicates a potentially critical role for AA in the pathobiology of MLBCL and CHL and thus an attractive therapeutic target for these tumors.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 197, Wednesday Morning