Intrinsic expression of drug resistance-associated factors in meningiomas

Meningiomas, commonly benign tumors, rarely display aggressive behavior by recurrences and invasion. In addition to surgery, irradiation is beneficial for recurrent. atypical. and malignant meningiomas. The role of chemothera py. however, remains controversial, although there is evidence that meningi omas respond well to adjuvant chemotherapy. A major obstacle in chemotherap y remains drug resistance with reduced cellular drug accumulation through m embrane efflux pumps, drug detoxification. and alterations in drug target s pecificity. In 84 classic. atypical, and malignant meningiomas, the immunoh istochemical expression profile of P-glycoprotein (P-gp), multidrug resista nce-associated protein (MRP), lung resistance-related protein (LRP), metall othionein, and topoisomerase II alpha were studied. All types of meningioma s showed constant expression of P-gp, LRP, MRP, and topoisomerase II alpha: metallothionein was found in 67% of the tumors. especially in atypical and malignant meningiomas. Furthermore. metallothionein, P-gp, LRP and topoiso merase II alpha were strongly expressed by normal and neoplastic vessels, w hich may confer to impaired penetration of therapeutic agents through the b lood-brain and blood-tumor barrier. Neither recurrent nor pre, iously irrad iated meningiomas revealed any significant difference to primary tumors. Th ese intrinsic drug resistances indicate that successful chemotherapy may re quire additional inhibition of these factors to be a promising approach in the management of meningiomas.