P60.01 Investigation of Aurora Kinase A as a Potential Biomarker of Radiation in Non-Small Cell Lung Cancer (NSCLC)

Abstract

Aurora Kinases belong to a family of serine/threonine kinases with three known subtypes: AURKA, Aurora B (AURKB) and Aurora C (AURKC) (Tao et al., 2008). Their overexpression is linked to tumorigenesis, chemotherapy, and radiation resistance. AURKA inhibition leading to enhanced radiosensitivity has been demonstrated in our laboratory. There is interest in determining whether the increased expression of AURKA is linked to patient survival. The purpose of this study is to examine the correlation between increased AURKA expression in patient biopsies and survival in patients with NSCLC. One hundred and one patients were recruited to a prospective study where the patient was offered radical and high dose palliative radiation for NSCLC—65% of patients presented with stage III and IV advanced disease. Archived biopsy samples collected before radiotherapy were stained for AURKA expression using immunohistochemistry. The tumour cells on each slide were counted and categorised as negative, borderline, weak or definite staining. The percentage ratio of staining on each slide between each category was recorded. The combined percentage of weak and definite categories in each slide were added and classified as a “positive stain” with borderline and negative categories a “negative stain”. The mean of the combinations of weak and definite stains in all slides was calculated (12.92%). Slides with a combined total percentage of weak and definite staining greater than 12.92% would be defined as AURKA positive. The mean staining of weak and definite slides was correlated with overall and progression-free survival. The median overall survival for patients entering the study was 266 days (8.8 months), 95% Confidence Interval (CI), 203 - 374 days). Median progression-free survival was 171 days (5.7 months (95% CI 116 - 279 days). There was no statistical difference in overall and progression-free survival between AURKA positive and AURKA negative biopsies. (figure1). The expression of AURKA did not result in significant differences in overall or progression-free survival.