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GROWTH FACTOR SIGNALLING PATHWAYS IN MENINGIOMAS IS COMMON AND PARTLY DEPENDS ON SUBTYPE ALLOWING FOR STRATIFICATION Free

INTRODUCTION: A significant minority of meningiomas are difficult to treat with surgery or radiotherapy, and there are limited chemotherapeutic alternatives. This study aims to better understand the pathways that are active in these tumours, in order to direct future treatment strategies. METHOD: We have investigated the expression of several growth factors and their signalling pathways in 30 meningiomas, using immunohistochemistry and Western blots. Expression was correlated with presumed NF2 gene status, using fluorescent in situ hybridisation to look for chromosome 22q loss. RESULTS: Membrane expression of VEGFR and PDGFR-beta was seen in 83% of tumours, Axl in 70%, EGFR in 50% and IGFR in 47%. Expression was similar in low and high grade tumours, but membrane EGFR expression was not seen in tumours showing chromosome 22q loss. Expression of the ligands IGF, NRG, VEGF, Gas 6, and downstream signalling proteins, Mek, Erk, Jnk and Akt, and pS6RP, was widespread. Our findings suggest that the majority of meningiomas express and show activation of multiple growth factor receptors and their downstream signalling pathways irrespective of tumour grade. CONCLUSION: In addition to previously reported receptors, Axl may also offer an attractive therapeutic target. Our findings also suggest that anti-EGFR based therapies may be less effective in meningiomas with 22q loss.