Decreased expression of the active subunit of the cystine/glutamate antiporter xCT is associated with loss of heterozygosity of 1p in oligodendroglial tumours WHO grade II.
OBJECTIVE
Oligodendroglial tumours with loss of heterozygosity on 1p (LOH1p) respond better to treatment than oligodendrogliomas without LOH. Previous reports have assigned a crucial role of glutamate metabolism to glioma growth and invasion. The aim was to study the protein expression of different glutamate transporters in relation to LOH1p in low-grade oligodendroglial tumours.


RESULTS
Seventeen oligodendrogliomas World Health Organization (WHO) grade II, 16 oligoastrocytomas WHO grade II and seven astrocytomas WHO grade II were examined. Eleven oligodendrogliomas and five oligoastrocytomas exhibited LOH1p. Immunoreactivity scores (IRS) for glutamate transporters excitatory amino acid transporter (EAAT)-1, -2 and -3 as well as the active cystine/glutamate antiporter subunit xCT were semiquantitatively rated by percentage of positive cells and intensity of immunoreactivity. Reactivity for xCT was lower in tumours with LOH1p than in those without (P = 0.03, Mann-Whitney U-test). No association was found between LOH status and IRS for EAAT-1, -2 or -3. High xCT immunoreactivity was associated with high expression of EAAT-1, -2 or -3.


CONCLUSIONS
Expression of xCT is significantly reduced in low-grade oligodendroglial tumours harbouring LOH1p. Further studies should investigate a potential beneficial effect by inhibiting xCT in low-grade gliomas.
Stockhammer
Florian
F
Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany. florian.stockhammer@charite.de
von Deimling
Andreas
A
van Landeghem
Frank K H
FK
D000328:Adult; D000368:Aged; D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis; D027182:Amino Acid Transport System y+ / Q000096:biosynthesis*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014944:World Health Organization
D027322:Amino Acid Transport System X-AG; D027182:Amino Acid Transport System y+; C118895:SLC7A11 protein, human