Oncotarget

Research Papers: Pathology:

Phospho-AXL is widely expressed in glioblastoma and associated with significant shorter overall survival

Julia Onken, Peter Vajkoczy _, Robert Torka, Claudia Hempt, Victor Patsouris, Frank L. Heppner and Josefine Radke

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Oncotarget. 2017; 8:50403-50414. https://doi.org/10.18632/oncotarget.18468

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Abstract

Julia Onken1,2, Peter Vajkoczy1, Robert Torka3, Claudia Hempt1, Victor Patsouris1, Frank L. Heppner2,4,5,6 and Josefine Radke2,4,6

1 Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany

2 Berlin Institute of Health (BIH), Berlin, Germany

3 Institute of Physiological Chemistry, Martin Luther University of Halle-Wittenberg, Halle/Saale, Germany

4 Department of Neuropathology, Charité - Universitätsmedizin Berlin, Berlin, Germany

5 Cluster of Excellence, NeuroCure, Berlin, Germany

6 German Cancer Consortium (DKTK), Heidelberg, Germany, Partner Site Charité Berlin, Berlin, Germany

Correspondence to:

Peter Vajkoczy, email:

Keywords: glioblastoma multiforme (GBM), receptor tyrosine kinase AXL (AXL), glomeroid tufts, overall survival, phospho-Axl (P-AXL), Pathology Section

Received: March 23, 2017 Accepted: May 10, 2017 Published: June 13, 2017

Abstract

Receptor tyrosine kinase AXL (RTK-AXL) is regarded as a suitable target in glioblastoma (GBM) therapy. Since AXL kinase inhibitors are about to get approval for clinical use, patients with a potential benefit from therapy targeting AXL need to be identified. We therefore assessed the expression pattern of Phospho-AXL (P-AXL), the biologically active form of AXL, in 90 patients with newly diagnosed GBM, which was found to be detectable in 67 patients (corresponding to 74%). We identified three main P-AXL expression patterns: i) exclusively in the tumor vasculature (13%), ii) in areas of hypercellularity (35%), or iii) both, in the tumor vasculature and in hypercellular areas of the tumor tissue (52%). Pattern iii) is associated with significant decrease in overall survival (Hazard ratio 2.349, 95% confidence interval 1.069 to 5.162, *p=0.03). Our data suggest that P-AXL may serve as a therapeutic target in the majority of GBM patients.


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