gms | German Medical Science

Objective: In spite of modern neurosurgical and radiosurgical strategies, meningiomas may recur and have a prolonged impact on the quality of life. So far effective chemotherapy protocols do not exist, in particular since molecular targets have not been identified. C-kit, a receptor tyrosine-kinase is a proto-oncogene in various tumors, blocking its function by the small molecule inhibitor imatinib leads to tumor responses. The goal of this study was to characterize the expression of c-kit in meningiomas and to analyze the impact of c-kit inhibition by imatinib in vitro.

Methods: Tissue micro-array analysis was performed on 346 formalin-fixed meningioma specimens. 10 fresh meningioma specimens were cultured in a three-dimensional spheroid model and these spheroids were incubated with imatinib (10µM) and paclitaxel (1mM) as positive control für 4 weeks. After 4 weeks a migration assay, MIB-staining and apoptose staining (TUNEL) (Immunostaining on cryoslides) was done in order to asses the biological effects of imatinib.

Results: 84% of meningiomas were positive for C-kit. Divided into the histological grades, the percentage rates were 83% for WHO I (253 specimen), 91% for WHO II (79 specimen) and 58% for WHO III (12 specimen). After 4 weeks of incubation, the meningioma spheroids demonstrated in the migration assay a 34.6% migration reduction with imatinib was compared to controls (paclitaxel: 76.3%). The rate of proliferating cells in the meningioma spheroids was 8.6% in the control group, 3.4% after imatinib treatment and 0% after palitaxel treatment. Imatinib was also able to induce apoptosis in the meningioma spheroids (36.4% apoptotic cells after imatinib treatment, 96% after paclitaxel treatment and 8.3% in the control experiments).

Conclusions: It was shown that a high percentage of meningiomas are C-kit positiv. In vitro is was possible to induce a biological effects using the C-kit inhibitor imatinib demonstrated in induction of apoptosis and reduction of proliferation. Migration of meningioma cells was also reduced by imatinib. Whether these effects are of clinical relevance remains forfurther in vivo studies to evaluate. In particular it has to be put into consideration that this proposed chemotherapy may be a long-term treatment whose long-term side effects are not well characterized so far.