Department of Neuropathology, Fondazione IRCCS Istituto Neurologico C. Besta, Via Celoria 11, 20133, Milan, Italy.
J Neurooncol. 2012 Oct;110(1):129-35. doi: 10.1007/s11060-012-0946-9. Epub 2012 Jul 26.
Epilepsy occurs in glioma, especially in low-grade glioma (LGG), but also in glioblastoma (GBM). In about 20 % of patients pharmacological treatment with anti-epileptic drugs (AEDs) fails. Refractory epilepsy is a multifactorial phenomenon not yet completely understood. The multidrug resistance phenotype was initially associated to P-glycoprotein (Pgp), an ATP-dependent transporter belonging to the same superfamily of multidrug resistance-associated proteins (MRPs). Glutathione-S-transferase-π (GST-π) is also involved in refractory epilepsy. In the present work we investigated the expression of Pgp, MRP1, MRP3 and GST-π in surgical specimens obtained from 35 patients with glioma and epilepsy. We observed MRP1 expression in tumor and endothelial cells (EC), MRP3 and Pgp expression mainly in ECs and GST-π predominantly in tumor cells (TC). MRP1 and MRP3 were more expressed in high grade glioma (HGG) than in LGG. In 6 cases we could compare tumor and periphery detecting the same MRP1 and Pgp expression, while MRP3 was mainly expressed in the tumor. We observed a trend of a better outcome in seizure control associated with a lower expression of MRP1 and MRP3. MRP3 was statistically more expressed in TCs of HGG than LGG (p = 0.0401) and more expressed in tumor than in periphery, in agreement with recent works that identify MRP3 as a potential target in GBM. Moreover, MRP3 was investigated in association with refractory epilepsy for the first time in our study and it was less expressed in patients with complete response to AEDs (p = 0.0550). Our preliminary data show an association between multidrug resistance transporters and refractory epilepsy in glioma.
癫痫发生在神经胶质瘤中，特别是在低级别神经胶质瘤（LGG）中，但也发生在胶质母细胞瘤（GBM）中。约 20%的患者对抗癫痫药物（AED）的药物治疗反应不佳。耐药性癫痫是一种多因素现象，尚未完全了解。多药耐药表型最初与 P-糖蛋白（Pgp）相关，Pgp 是一种属于多药耐药相关蛋白（MRPs）超家族的 ATP 依赖性转运蛋白。谷胱甘肽-S-转移酶-π（GST-π）也与耐药性癫痫有关。在本工作中，我们研究了 35 例神经胶质瘤伴癫痫患者手术标本中 Pgp、MRP1、MRP3 和 GST-π 的表达。我们观察到肿瘤和内皮细胞（EC）中 MRP1 的表达，EC 中主要表达 MRP3 和 Pgp，肿瘤细胞（TC）中主要表达 GST-π。高级别神经胶质瘤（HGG）中 MRP1 和 MRP3 的表达高于低级别神经胶质瘤（LGG）。在 6 例患者中，我们可以比较肿瘤和肿瘤周围组织，检测到相同的 MRP1 和 Pgp 表达，而 MRP3 主要在肿瘤中表达。我们观察到，与 MRP1 和 MRP3 表达较低相关的癫痫控制更好的趋势。MRP3 在 HGG 的 TC 中的表达明显高于 LGG（p = 0.0401），在肿瘤中的表达也高于肿瘤周围组织，这与最近的研究工作一致，这些研究工作将 MRP3 确定为 GBM 的潜在靶点。此外，在本研究中，MRP3 是首次与耐药性癫痫相关联进行研究的，在对 AED 完全有反应的患者中表达较低（p = 0.0550）。我们的初步数据表明，在神经胶质瘤中，多药耐药转运蛋白与耐药性癫痫之间存在关联。
