Cyclooxygenase (COX)-1 expressing macrophages/microglial cells and COX-2 expressing astrocytes accumulate during oligodendroglioma progression.
Cyclooxygenases (COX, prostaglandin endoperoxide synthases, PGG/H synthases) are potent mediators of edema, impeding blood flow and immunomodulation in the pathologically altered brain. Two COX iso-enzymes have been associated with brain disease, the constitutively expressed COX-1 and the cytokine-inducible COX-2. We have used single and double labeling immunohistochemistry to analyse COX-1 and COX-2 expression in twenty-six primary WHO grade II oligodendrogliomas, sixteen primary WHO grade III anaplastic oligodendrogliomas, twenty-seven matched recurrences and ten neuropathologically unaltered brains. COX-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of COX-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in primary anaplastic oligodendrogliomas (P<0.0001) and in anaplastic oligodendroglioma relapses (P=0.011). Patients with low COX-1 labeling scores in the primary tumors had significantly longer time to progression and overall survival (P=0.0285) than those with high COX-1 labeling scores. COX-2 immunoreactivity was predominantly observed in disseminated neurons and astrocytes. In glioblastoma multiforme relapses, accumulation of COX-2 expressing astrocytes was observed surrounding areas of focal necrosis. The number of COX-2 expressing astrocytes was significantly (P=0.0471) lower in primary oligodendrogliomas than in high grade oligodendroglioma relapses. These data provide convincing evidence for the differential accumulation of cyclooxygenase isoforms during oligodendroglioma progression in vivo.
Deininger
M H
MH
Institute of Brain Research, University of Tuebingen, Medical School, Tuebingen, Germany. martin.deininger@uni-tuebingen.de
Meyermann
R
R
Trautmann
K
K
Morgalla
M
M
Duffner
F
F
Grote
E H
EH
Wickboldt
J
J
Schluesener
H J
HJ
D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D017628:Microglia / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D009837:Oligodendroglioma / Q000378:metabolism* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases