ARD1 Expression in Diffuse Large B-Cell Lymphoma with Clinical Correlation
Li Li, Katsiaryna Laziuk, Christine Sheehan, Tipu Nazeer. Albany Medical College, Albany, NY
Background: Arrest-defect-1 protein (ARD1) is an acetyltransferase that catalyses N-a-acetylation in yeast, both N-a-acetylation and e-acetylation in mammalian cells. It has been shown that ARD1 is involved in a variety of cellular functions, including proliferation, apoptosis, autophagy and differentiation. Deregulation of ARD1 is associated with tumorigenesis and neurodegenerative disorder. Although human ARD1 protein has been reported to be expressed extensively in cancer tissues including adenocarcinoma and squamous carcinoma from various organs, its expression has not been widely studied in clinical specimens of hematologic malignancies.
Design: Formalin-fixed, paraffin embedded sections from 82 Diffuse Large B-cell Lymphomas (DLBCLs) were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) using mouse monoclonal ARD1 antibody (Abnova, Jhongli, Taiwan). Cytoplasmic and nuclear immunoreactivity was semiquantitatively assessed in all cases. Scoring was based on staining intensity (weak, moderate, intense) and percentage of positive cells (focal <= 10%, regional 11-50%, diffuse >50%). Results were correlated with clinicopathologic variables.
Results: Cytoplasmic ARD1 immunoreactivity was observed in 80/82 (98%) cases; with an intense diffuse pattern noted in 48/82 (59%) cases. Intense diffuse cytoplasmic ARD1 immunoreactivity correlated with advanced stage [16/24 (67%) advanced stage vs 12/30 (40%) early stage, p=0.05; stage available in 54 cases], nodal disease [26/35 (74%) nodal versus 22/47 (47%) extranodal, p=0.012], and disease remission [13/17 (77%) in remission versus 1/5 (20%) not in remission, p=0.021, remission status available in 22 cases]. Nuclear ARD1 immunoreactivity was observed in 27/82 (33%) cases and correlated with early stage [16/30 (53%) early stage versus 5/24 (21%) advanced stage, p=0.015] and extranodal disease [20/47 (43%) extranodal versus 7/35 (20%) nodal, p=0.032].
Conclusions: Cytoplasmic ARD1 expression was identified in the majority of DLBCLs. Intense diffuse cytoplasmic ARD1 immunoreactivity is associated with advanced stage, nodal disease and disease remission. On the contrary, while nuclear ARD1 immunoreactivity is expressed in fewer DLBCLs, it is associated with early stage and extranodal disease. The differing localization and correlation of ARD1 immunoreactivity in this study supports recent reports associating proteins with different biological functions according to their subcellular localization. Further study appears warranted.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 198, Tuesday Afternoon