ARD1 Expression Correlates with Favorable Prognostic Variables in Invasive Mammary Carcinoma (MC)
Guilian Niu, Bhaskar VS Kallakury, Ann B Boguniewicz, Christopher B Sheehan, Christine E Sheehan, Jeffrey S Ross. Albany Medical College, Albany, NY; Georgetown University Hospital, Washington, DC
Background: The arrest defective 1 (ARD1) protein is an acetyltransferase linked to proliferation and apoptosis in mammalian cells and recently associated with several human tumors. Although ARD1 expression has been previously demonstrated in MC by IHC, the prognostic significance of ARD1 in clinical MC specimens has not been previously studied.
Design: Formalin-fixed, paraffin-embedded tissue sections from 115 cases MC [76 ductal carcinomas (IDC) and 39 lobular carcinomas (ILC)] were immunostained by automated method (Ventana Medical Systems Inc., Tucson, AZ) using mouse monoclonal ARD1 antibody (Abnova, Jhongli, Taiwan). Nuclear and cytoplasmic immunoreactivity were scored based on intensity (weak, moderate, intense) and percentage of positive cells (focal <= 10%, regional 11-50%, diffuse >50%) in tumor (T), in situ disease (I) when present, and adjacent benign epithelium (B). An additive index was calculated and cases were assessed as T=0/B=0, T=B, T>B, T < B; and I=0/B=0, I=B, I > B, I < B). Results were correlated with clinicopathologic variables.
Results: Nuclear immunoreactivity was noted in 97/115 (84%) cases overall with T < B [73/115 (63%)], T=B [24/115 (21%)], T=0/B=0 [18/115 (16%)]; I=B [27/54 (50%)], IB [1/54 (2%)] cases. Loss of nuclear ARD1 immunoreactivity correlated overall with tumor type [T < B in 72% ILC vs 59% IDC, T=B in 8% ILC vs 28% IDC, T=0/B=0 in 21% ILC vs 13% IDC p=0.04]; overall with tumor stage [T < B in 65% early vs 56% advanced, T=B in 28% early vs 13% advanced, T=0/B=0 in 7% early vs 31% advanced, p=0.003] and within the IDC subgroup [T < B in 60% early vs 54% advanced, T=B in 36% early vs 17% advanced, T=0/B=0 in 4% early vs 29% advanced, p=0.007]; and overall with ER status [T < B in 69% ER+ vs 54% ER-, T=B in 22% ER+ vs 20% ER-, T=0/B=0 in 9% ER+ vs 27% ER-, p=0.046]. Within the 54/115 (47%) cases with in situ disease present, in all IB 55/115 (48%), T < B 4/115 (3%); I=B 42/54 (78%) and I>B 12/54 (22%) cases with no significant correlations. On multivariate analysis, disease recurrence (p=0.002) independently predicted overall survival.
Conclusions: Loss of nuclear ARD1 expression is associated with favorable prognostic variables in MC including ILC subtype, early pathologic stage and ER+ status. Further study of ARD1 in MC appears warranted.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 18, Wednesday Afternoon