Abstract 1151: Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis.

Introduction: Approximately half of all colorectal cancer (CRC) patients die as a consequence of metastases. Hemihepatectomy, occasionally in combination with radiofrequency ablation (RFA), is the only curative treatment available for patients with CRC liver metastases (CRCLM). Patient eligibility is based on established prognostic clinicopathological variables, however, 70% of patients still die within 5 years indicating that better prognostic markers are needed. Aurora kinase A (AURKA) is a driver of 20q gain-associated tumor progression and is associated with disease recurrence in stage III CRC patients. AIM: This study aimed to investigate the prognostic value of AURKA protein expression in liver metastases of CRC patients who underwent hemihepatectomy with curative intent. Patients and Methods: Tissue microarrays (TMAs) were generated from formalin-fixed paraffin-embedded CRCLM of 507 patients who underwent hemihepatectomy in the Netherlands between 1990 and 2010. Matched primary CRC tissue was collected of 234 patients. TMAs were stained for AURKA by immunohistochemistry, nuclear expression of neoplastic cells was assessed and subsequently associated with patient overall survival (OS) in a training and validation set. Results: High AURKA expression in CRCLM was associated with poor OS in a univariate analysis (HRR 1.68; 95%CI 1.04-2.73; P=0.03) and upon correction for established prognostic clinicopathological variables (HRR 1.77; 95%CI 1.02-3.08; P=0.04). Furthermore, AURKA expression in liver metastases was correlated to its expression in corresponding primary CRC (P=0.0002). Conclusion and Discussion: AURKA protein expression is a molecular biomarker with prognostic value for CRC patients with liver metastasis, independent of established clinicopathological variables. This study opens novel opportunities to investigate AURKA inhibitors for personalized therapy. Citation Format: Jeroen A C M Goos, Veerle M H Coupe, Begona Diosdado, Pien M. Delis-van Diemen, Cemile Karga, Jeroen A.M. Belien, Beatriz Carvalho, M. Petrousjka van den Tol, Henk M W Verheul, Albert A. Geldof, Gerrit A. Meijer, Otto S. Hoekstra, Remond J A Fijneman. Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1151. doi:10.1158/1538-7445.AM2013-1151