PO-246 AXL receptor tyrosine kinase expression as a prognostic marker and therapeutic target in neuroendocrine tumours

Abstract

IntroductionNeuroendocrine tumours (NETs) present a clinical challenge due to their late presentation, limited treatment options and a lack of accurate biomarkers to guide their management. Increasing evidence has confirmed the oncogenic potential of the receptor tyrosine kinase Axl, which is implicated in several hallmarks of cancer progression. This study aimed to evaluate the prevalence, prognostic role and therapeutic potential of Axl expression and its ligand Gas6 in NETs.Material and methodsTissue microarray blocks were constructed from a consecutive cohort of 54 patients with surgically resected NETs. The prevalence of the expression of Axl and Gas6 as well as markers of hypoxia were identified and correlated with clinicopathologic features and overall survival. To test the hypothesis of whether Axl is involved in the metastatic progression of NETs, immunostaining for Axl and Gas6 was evaluated in paired primary and metastatic tumour specimens in a group of post mortem cases (n=7) with adequately preserved tissues.Results and discussionsIn the 54 consecutive patients, n=46 (85%) presented with a pancreatic primary, n=24 (44%) were well-differentiated tumours and 35% were metastatic. Axl/Gas6 overexpression was identified in n=28 (52%) of the resection specimens.In isogeneic primary/metastatic NETs, Axl was overexpressed in 29% of primary tumour specimens and 61% of metastatic deposits and interestingly, Gas6 was also expressed in 29% of primaries and 61% of metastases. Axl and Gas6 expression did not correlate with VEGF-A or CaIX, nor was it predictive of overall survival in univariate analyses. However, Axl and Gas6 overexpression correlated significantly with decreased HiF1α expression levels.ConclusionOverexpression of Axl and Gas6 was found in >50% of NETs and correlated with decreased HiF1α expression. However, it did not influence patient’s overall survival.