Aurora A Kinase (AURKA) Expression and Clinical Outcome in Invasive Mammary Carcinoma.
Jennifer Garbaini, Kelly Ann Kim, Christine E Sheehan, Ann B Boguniewicz, Jeffrey S Ross. Albany Medical College, NY
Background: AURKA, a serine/threonine kinase associated with cell proliferation and mitotic spindle formation, has been studied in a variety of solid tumors including mammary carcinoma. In the following study, AURKA expression was evaluated based on cell localization and clinic-pathologic parameters including patient survival.
Design: Formalin-fixed, paraffin-embedded tissue sections from 177 cases of invasive mammary carcinoma (128 ductal carcinomas (IDC) and 49 lobular carcinomas (ILC) were immunostained by automated methods (Ventana Medical Systems Inc., Tucson, AZ) using a mouse monoclonal antibody to Aurora A (Abcam, Cambridge, MA). Cytoplasmic and nuclear immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
Results: Both cytoplasmic and nuclear AURKA immunoreactivity was observed. Cytoplasmic AURKA overexpression was noted in 102/177 (57%) tumors; 77/128 (60%) IDC and 25/49 (51%) ILC. AURKA cytoplasmic overexpression correlated overall with high grade (p=0.002) and advanced stage (p=0.039); and within the IDC subgroup correlated with high grade (p=0.005), advanced stage (p=0.007) and showed a trend toward association with positive lymph node status (p=0.066). Nuclear AURKA overexpression was noted in 111/177 (63%) tumors; 72/128 (60%) IDC and 39/49 (80%) ILC and correlated with ILC tumor type (p=0.004), and overall with low grade (p=0.05), early stage (p=0.039), ER positive status (p=0.001), PR positive status (p=0.03), and HER2 negative status (p=0.014). There was no correlation between cytoplasmic and nuclear expression. On multivariate analysis, early age at diagnosis, advanced stage and disease recurrence were independent predictors of shortened survival.
Conclusions: AURKA cytoplasmic overexpression was associated with high grade and advanced stage in both invasive ductal and lobular carcinoma. Nuclear AURKA overexpression correlated with low grade and early stage carcinomas, ER and PR positive status, and HER2 negative status. Loss of localization of AURKA from the nuclear mitotic apparatus is thus linked to high grade carcinoma. Further study of AURKA expression in mammary carcinoma and the continued exploration of AURKA inhibitors in breast cancer clinical trials appear warranted.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 39, Monday Morning