Deininger M H, Meyermann R, Trautmann K, Morgalla M, Duffner F, Grote E H, Wickboldt J, Schluesener H J
Institute of Brain Research, University of Tuebingen, Medical School, Tuebingen, Germany.
Brain Res. 2000 Dec 1;885(1):111-6. doi: 10.1016/s0006-8993(00)02978-4.
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.
环氧化酶(COX,前列腺素内过氧化物合酶,PGG/H合酶)是水肿的强效介质,在病理改变的大脑中会阻碍血流并调节免疫。两种COX同工酶与脑部疾病相关,即组成型表达的COX-1和细胞因子诱导型COX-2。我们使用单标记和双标记免疫组织化学分析了26例世界卫生组织(WHO)II级原发性少突胶质细胞瘤、16例WHO III级间变性少突胶质细胞瘤、27例配对复发肿瘤以及10例神经病理学未改变的大脑中COX-1和COX-2的表达情况。COX-1免疫反应主要见于巨噬细胞/小胶质细胞。原发性少突胶质细胞瘤中表达COX-1的巨噬细胞/小胶质细胞数量明显低于原发性间变性少突胶质细胞瘤(P<0.0001)和间变性少突胶质细胞瘤复发肿瘤(P=0.011)。原发性肿瘤中COX-标记评分低的患者比评分高的患者进展时间和总生存期明显更长(P=0.0285)。COX-2免疫反应主要见于散在的神经元和星形胶质细胞。在多形性胶质母细胞瘤复发中,在局灶性坏死区域周围观察到表达COX-2的星形胶质细胞聚集。原发性少突胶质细胞瘤中表达COX-2的星形胶质细胞数量明显低于高级别少突胶质细胞瘤复发肿瘤(P=0.0471)。这些数据为体内少突胶质细胞瘤进展过程中环氧化酶同工型的差异积累提供了令人信服的证据。