Expression of multidrug transporters in dysembryoplastic neuroepithelial tumors causing intractable epilepsy.
OBJECTIVE
Dysembryoplastic neuroepithelial tumors (DNT) are relatively benign brain lesions that often cause medically intractable epilepsy. There is mounting evidence that multidrug transporters such as P-glycoprotein (P-gp) or multidrug resistance-associated proteins (MRP) play an important role in the development of resistance to antiepileptic drugs (AED).


METHODS
In the present study, we examined the expression of several multidrug transporters in 14 cases of DNT. The peritumoral brain tissue as well as 9 cases of arteriovenous malformations (AVM) served as controls. P-gp, MRP2, MRP5 and breast cancer resistance protein (BCRP) expression was evaluated qualitatively and quantitatively using immunohistochemistry.


RESULTS
All transporters were overexpressed quantitatively in DNT, but each revealed a different labeling pattern. P-gp and BCRP were predominantly located in the endothelium of brain vessels. MRP5 was detected primarily in endothelial cells, but notably also in neurons. The expression of P-gp, MRP2 and MRP5 was low in AVM, whereas BCRP demonstrated strong staining. Examination of MDR1 gene polymorphisms revealed no correlation with P-gp expression whereas the MRP2 exon 10 G1249A polymorphism was associated with different MRP2 labelling.


CONCLUSIONS
Our results show that multidrug transporters are overexpressed in DNT. This finding supports the view that several of these transport proteins may play an important role in the mechanisms of drug resistance in epileptic brain tissue.
Vogelgesang
S
S
Department of Neuropathology, University of Greifswald, Germany. sivogelg@uni-greifswald.de
Kunert-Keil
C
C
Cascorbi
I
I
Mosyagin
I
I
Schröder
E
E
Runge
U
U
Jedlitschky
G
G
Kroemer
H K
HK
Oertel
J
J
Gaab
M R
MR
Pahnke
J
J
Walker
L C
LC
Warzok
R W
RW
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000098:blood supply / Q000150:complications / Q000378:metabolism*; D002648:Child; D004351:Drug Resistance / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D004827:Epilepsy / Q000209:etiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D018302:Neoplasms, Neuroepithelial / Q000098:blood supply / Q000150:complications / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D027425:ATP-Binding Cassette, Sub-Family C Proteins