Arrest Defective 1 (ARD1) Protein Expression Is Associated with Clinical Outcome in Colorectal Cancer (CRC)
Osama Elkadi, Christine Sheehan, Jeffrey Ross, David Jones. Albany Medical College, Albany, NY
Background: Arrest defective 1 (ARD1) protein is an acetyltransferase that has been linked with proliferation and apoptosis in mammalian cells. Although ARD1 expression has been demonstrated in CRC, the prognostic significance of ARD1 in clinical CRC specimens has not been previously studied.
Design: Formalin-fixed, paraffin embedded sections from 156 CRC were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) with mouse monoclonal ARD1 antibody (Abnova, Jhongli, Taiwan). Nuclear and cytoplasmic immunoreactivity was semiquantitatively assessed in invasive tumor cells for all cases. Scoring was based on staining intensity (weak, moderate, strong) and percentage of positive cells (focal <= 10%, regional 11-50%, diffuse >50%). Results were correlated with clinicopathologic variables.
Results: Any level of nuclear ARD1 expression was noted in 121/156 (78%) tumors. Intense diffuse nuclear ARD1 overexpression was noted in 38/156 (24%) tumors and correlated with advanced AJCC stage [23/74 (31%) stage III/IV and 14/79 (18%) stage I/II; p=0.05], mucin production [15/33 (46%) with mucin vs 15/60 (25%) without mucin, p=0.043; mucin status available in 93 cases] and shortened survival on Cox univariate analysis (p=0.03). Any level of cytoplasmic ARD1 expression was noted in 154/156 (99%) tumors. Intense diffuse cytoplasmic ARD1overexpression was noted in 73/156 (47%) tumors and correlated with advanced AJCC stage [41/74 (55%) stage III/IV and 31/79 (40%) stage I/II; p=0.045). There was no significant co-expression of subcellular localization patterns. On multivariate analysis, positive lymph node status (p<0.0001) and nuclear ARD1 overexpression (p=0.05) were independent predictors of overall survival.
Conclusions: Both nuclear and cytoplasmic ARD1 expression are biomarkers of adverse prognosis in CRC. Nuclear ARD1 overexpression is an independent predictor of overall survival in CRC. Further study of ARD1 expression and its potential as a target of therapy for CRC appears warranted.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 101, Monday Morning