Article
Anaplastic meningiomas WHO grade III lack of somatic AKT1-mutations and show an overexpression of EGF receptors
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Authors
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Tareq A. Juratli
- Klinik und Poliklinik für Neurochirurgie
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Ralf Wiedemuth
- Klinik und Poliklinik für Neurochirurgie
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Kathrin D. Geiger
- Institut für Pathologie und Neuropathologie, Carl Gustav Carus Universitätsklinikum, Dresden
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Achim Temme
- Klinik und Poliklinik für Neurochirurgie
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Matthias Kirsch
- Klinik und Poliklinik für Neurochirurgie
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Gabriele Schackert
- Klinik und Poliklinik für Neurochirurgie
| Published: | June 2, 2015 |
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Outline
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Objective: Our knowledge about molecular targets in anaplastic meningiomas WHO grade III (AM °III) is limited. The AKT1 mutation was newly described in a subset of meningioma patients and inhibitors of this mutation have shown promise in clinical trials in multiple cancer types. Therefore, we sought to determine the frequency of the AKT1 mutation as well as the expression level of multiple growth factor receptors in a large series of patients with AM WHO °III.
Method: Patients with AM °III were tested for the AKT1 (E17K) mutation using PCR technique. Additionally, the expression level of the epidermal growth factor receptor (EGFR), the platelet derived growth factor receptor 1alpha (PDGFR) and the vascular endothelial growth factor receptor (VEGFR) was detected by immunohistochemistry (IHC) using the indirect peroxidase technique on tissue multi arrays (TMA) of paraffin-embedded specimens. TMA samples were chosen on the basis of viewed full size slides. Staining was evaluated using a semi-quantitative scoring system. Chi-square test was used for statistical evaluation.
Results: We identified 22 AM °III patients with 45 tumors (median follow-up of 8 years). None of the examined 45 tumor samples in this cohort showed an AKT1 mutation (0%). Regarding the IHC, recurrent anaplastic meningiomas showed increasing proliferation with each recurrence. Overexpression of EGFR was associated with malignancy (p<0.01) and increased with recurrence (median score 2.3). The median overall survival rate for patents with EGFR overexpression was 2.2 years. In contrast, the overall survival of patients with low EGFR expression was not reached yet (p<0.05). While PDGFR and VEGFR scores were high in malignant tumors, the difference in comparison with benign meningiomas was not significant. A further finding is a marked survival benefit in our patients cohort in respect to the extent of resection when repeated operations were performed (p=0.025).
Conclusions: Somatic AKT1 mutations are absent in anaplastic meningiomas WHO grade III. Additionally, our data demonstrate that the overexpression of EGFR in anaplastic meningiomas makes this receptor valuable as a therapeutic target for the treatment of inoperable tumors.
