Multidrug resistance gene (MDR 1) expression in neuro-axial tumours of children and young adults

Abstract

Drug resistance in many cancers outside the CNS has been associated with over-expression of the multidrug resistance gene (MDR1), which codes for the transmembrane efflux pump P-glycoprotein (Pgp). To determine whether tumours of the neuroaxis over-express MDR1 and to identify the site of Pgp expression we examined 50 tumour specimens from 46 children and young adults using immunocytochemistry. Pgp was not expressed by any neoplastic cells, but was detected in die endothelium of tumour blood vessels in 35 of the 50 samples (70%). 11/35 (31%) were Pgp positive in the majority of vessels, 11/35 (31%) in a proportion, but < 50% of vessels, and 13/35 (37%) in one or two vessels. Pgp was also detected in surrounding normal brain capillaries. MDR1 may play a role in the chemoresistance of neuro-axial rumours either by its expression in the normal blood-brain barrier or by forming a blood-tumour barrier. The proportion of vessels expressing Pgp may determine the degree of resistance.

Key Words:

• Brain neoplasm
• chemotherapy
• drug resistance
• immunochemistry