gms | German Medical Science

Objective: Receptor tyrosine kinase AXL (RTK-AXL) is regarded as suitable target in glioma therapy. Here we evaluate the expression and localization of the biological active RTK-AXL (P-AXL) in human glioblastoma (GBM) tissue in order to define a suitable subgroup for future anti-AXL therapy.

Methods: We analyzed 100 tissue samples from newly diagnosed glioblastoma patients according to their P-AXL expression. The tissue was analyzed in terms of P-AXL expression by immunohistochemistry and immunofluorescence, antibody specificity has been proven with positive and negative controls. Co-staining of P-AXL and mesenchymal markers like vimentin and fibronectin was performed. Results were correlated with survival data.

Results: We stained a total of 100 patients and showed that P-AXL is expressed in each patient. We identified three main distribution patterns within the tumor. In 9% of patients P-AXL was found exclusively in perivascular/ vascular regions, in 91% P-AXL was expressed in hypercellular tumor tissue, pseudopalisades or vessels. P-AXL is found in mesenchymal-like areas and is co-localized with mesenchymal markers like vimentin and fibronectin. Expression of P-AXL in tumor tissue and tumor vasculature is associated with a significant decreased overall survival (Hazard ratio 2.349, 95% confidence interval 1.069 to 5.162, *p=0.03).

Conclusion: The broad expression of P-AXL among our patient collective and impaired survival in these patients strongly suggest that P-AXL serves as a target in the majority of GBM patients. Its role in EMT (epithelial to mesenchymal transition) and (neo-) vascularization of GBMs needs to be further investigated.