PO-490 Expression of cortactin and focal adhesion kinase in early stages of laryngeal tumorigenesis and clinical application for cancer risk-stratification

Abstract

IntroductionCortactin (CTTN) and the Focal Adhesion Kinase (FAK) are two major candidate genes to respectively drive 11q13- and 8q24-associated aggressive behaviour in various cancers. Recent evidence uncovered their clinical relevance in early stages of tumorigenesis as promising biomarkers for cancer risk assessment.Material and methodsUsing a multicenter validation study CTTN and FAK expression was evaluated by immunohistochemistry in a cohort of 109 patients with laryngeal precancerous lesions, and correlated with clinicopathologic parameters and laryngeal cancer risk. The pathophysiological role of CTTN and FAK was further investigated using functional studies in cellular models.Results and discussionsIncreased CTTN and FAK expression was detected in 49 (41%) and 35 (32%) laryngeal dysplasias, respectively. Univariate Cox analysis showed that CTTN and FAK expression but not histological grading were significantly associated with both recurrence risk and laryngeal cancer risk. Patients carrying strong CTTN- or FAK-expressing lesions experienced the highest laryngeal cancer incidence (log-rank p<0.001). In multivariate stepwise analysis, FAK expression (HR=13.91, 95% CI 4.82–40.15; p<0.001) and alcohol consumption (HR=2.22, 95% CI 1.17–4.20; p=0.014) were significant independent predictors of laryngeal cancer development. Targeting FAK by either RNAi or pharmacological inhibitors effectively blocked cell growth, colony formation and invasion into 3D collagen matrices.ConclusionCTTN and FAK emerge as powerful predictors of laryngeal cancer risk beyond histological grading, thus encouraging their clinical application as complementary markers for risk-stratification. Furthermore, our findings unveil that pharmacological targeting of FAK could constitute a promising therapeutic strategy for HNSCC prevention and treatment.