Prognostic Significance of Aurora A Kinase (AURKA) Expression in Non Small Cell Lung Cancer (NSCLC).
Li Li, Christine E Sheehan, Jeffrey S Ross. Albany Medical College, NY
Background: AURKA is a serine/threonine kinase that stimulates mitotic progression through the regulation mitotic spindles and centrosomes. AURKA inhibitors are in early clinical trials for the treatment of solid tumors.
Design: Formalin-fixed, paraffin embedded sections from 111 NSCLC, including 30 squamous cell carcinomas (SCC), 44 adenocarcinomas (AC), and 37 either pure bronchioloalveolar carcinomas (BAC) or AC with BAC features were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) with a monoclonal antibody to Aurora A (Abcam, Cambridge, MA). Cytoplasmic and nuclear immunoreactivity was semiquantitatively assessed in the tumor for 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: Both cytoplasmic and nuclear AURKA immunoreactivity was observed. Overexpression was noted in 60/111 (54%) tumors overall and correlated with tumor type [30% SCC vs. 11% AC vs. 32% BAC, p=0.05], small tumor size (<= 3.0 cm) [p=0.04], male gender [p=0.02], and shortened survival [p=0.049]. Within the SCC subgroup, nuclear AURKA overexpression correlated with small tumor size (<= 3.0 cm) [p=0.005], male gender [p=0.05] and shortened survival [p=0.03]; while cytoplasmic overexpression showed a trend toward association with early stage [p=0.10] and node negative [p=0.09] disease. Within the BAC subgroup, cytoplasmic Aurora overexpression correlated with advanced stage [p=0.02], while showing a trend toward correlation with node positive [p=0.10] disease. On multivariate analysis, only disease stage independently predicts shortened survival.
Conclusions: AURKA is expressed in the majority of NSCLC and is significantly associated with histologic subtype and patient survival. Continued clinical trials of AURKA inhibitors for the treatment of NSCLC appear warranted.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 256, Tuesday Afternoon