Andersson U, Malmer B, Bergenheim A T, Brännström T, Henriksson R
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Clin Neuropathol. 2004 Jan-Feb;23(1):21-7.
Brain tumors, in general, display a multidrug-resistant phenotype. This study evaluated the immunohistochemical expression and distribution of P-glycoprotein (Pgp), multidrug resistance protein (MRP1), lung resistance protein (LRP) and O6 methylguanine-DNA methyltransferase (MGMT) in low- and high-grade astrocytoma, oligodendroglioma and in different subgroups of meningioma. The results revealed a marked heterogeneity in the expression and distribution among the analyzed tumors. In astrocytoma and oligodendroglioma, Pgp and MRP1 were observed in the capillary endothelium and in scattered tumor cells, whereas LRP occurred only in tumor cells. A pronounced expression of MGMT was found independent of the histopathological grade. An enhanced expression of MRP1 and LRP in astrocytoma and oligodendroglioma were more often evident in older patients (> 50 years). Survival analysis suggested a markedly decreased overall survival for patients suffering from low-grade glioma overexpressing Pgp. In meningioma, a heterogeneous expression of Pgp, MRP1, LRP and MGMT was seen with the most prominent staining localized to the capillary endothelium. Pgp was significantly more often overexpressed (p < 0.05) in transitional compared to meningothelial meningioma. The marked heterogeneity in the expression suggests that analysis of these factors can be of importance in the selection of individualized chemotherapy, regardless of tumor type.
一般来说，脑肿瘤呈现多药耐药表型。本研究评估了P-糖蛋白（Pgp）、多药耐药蛋白（MRP1）、肺耐药蛋白（LRP）和O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）在低级别和高级别星形细胞瘤、少突胶质细胞瘤以及不同亚组脑膜瘤中的免疫组化表达和分布。结果显示，在所分析的肿瘤中，这些蛋白的表达和分布存在显著异质性。在星形细胞瘤和少突胶质细胞瘤中，Pgp和MRP1在毛细血管内皮细胞和散在的肿瘤细胞中可见，而LRP仅出现在肿瘤细胞中。MGMT的表达明显，且与组织病理学分级无关。在年龄较大（>50岁）的患者中，星形细胞瘤和少突胶质细胞瘤中MRP1和LRP的表达增强更为常见。生存分析表明，低级别胶质瘤中过表达Pgp的患者总生存期显著降低。在脑膜瘤中，Pgp、MRP1、LRP和MGMT呈现异质性表达，最显著的染色定位于毛细血管内皮细胞。与脑膜内皮型脑膜瘤相比，过渡型脑膜瘤中Pgp过表达更为常见（p<0.05）。这些蛋白表达的显著异质性表明，无论肿瘤类型如何，分析这些因素对于个体化化疗方案的选择可能具有重要意义。
