Abstract 721: Expression of Aurora A and Phospho-Aurora-A is predictive of survival in patients with head and neck cancer

Abstract

Abstract Introduction: The Aurora kinases represent a family of serine/threonine kinases important in regulating cell cycle progression. Aurora-A is required for centrosome function and mitotic spindle assembly. Aurora-A phosphosphorylation supports the activity of many proteins involved in cell proliferation and survival, including important EGFR effectors such as AKT and RAS. High expression of Aurora A has been shown in patients with breast, lung, gastrointestinal, genitourinary, and gynecological cancers. The Aurora kinases are known to promote tumor formation and progression, which has led investigators to develop multiple inhibitors of Aurora kinases for clinical use. The expression of Aurora-A kinase in head and neck cancers is not well understood. We assessed the overall survival (OS) for a cohort of patients with squamous cell carcinoma of the head and neck (SCCHN) based upon Aurora-A and phospho-Aurora-A kinase expression (reflecting active Aurora-A). We also related this to SCCHN subtype, using p16 expression as a surrogate for human papillomavirus association, because of the recognition that p16 + cancers have far superior prognosis. Methods: Tumor tissue from 89 patients with SCCHN operated on at the Fox Chase Cancer Center was analyzed for Aurora-A and phospho-Aurora-A expression. Aurora kinase expression was determined using AQUATM, with the median values used to distinguish over-expressers. Aurora-A and phospho-Aurora-A expression was correlated with T and N stage and OS, in p16+ versus p16- tumors The p16 status was determined by immunohistochemistry. Results: T stage was inversely related to Aurora-A expression when adjusted for p16 status (Spearman's rho -0.24, p = 0.04). Aurora-A expression was not related to N stage (Spearman's rho -0.03, p = 0.79). OS was 36 months for over-expressers of Aurora-A and 92 months for patients with low levels of Aurora-A expression (HR 1.9, 95% CI 1.05-3.46). 20 patients were positive for p16 by IHC. There was no difference in survival amongst p16 positive patients based on Aurora-A expression (53.3 months vs 57.2 months, p = 0.679). Amongst the 69 p16 negative patients, OS was 93.6 months for patients with low levels of Aurora-A expression and 35.9 months for those with elevated levels of Aurora-A (HR 1.84, 95% CI 0.89-3.79). There was a trend towards improved survival in patients with lower levels of phospho-Aurora-A expression (63.9 vs 57.6 months, p = 0.129). Conclusions: Increased expression of Aurora-A in this cohort of SCCHN patients is associated with a significant decrease in OS. Increased expression of Aurora-A in patients with p16 positive tumors does not seem to impact survival, though the number of patients was small. Aurora-A represents a possible therapeutic target in patients with SCCHN. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 721. doi:1538-7445.AM2012-721