Multidrug resistance proteins expression in glioma patients with epilepsy

Abstract  

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.

• Content Type Journal Article
• Category Clinical Study - Patient Study
• Pages 1-7
• DOI 10.1007/s11060-012-0946-9
• Authors
  • Chiara Calatozzolo, Department of Neuropathology, Fondazione IRCCS Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy
  • Bianca Pollo, Department of Neuropathology, Fondazione IRCCS Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy
  • Andrea Botturi, Department of Neuro-oncology, Fondazione IRCCS Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy
  • Loredana Dinapoli, Center for Brain Tumor-related Epilepsy, Istituto Nazionale Tumori "Regina Elena", Via Elio Chianesi 53, 00144 Rome, Italy
  • Mariantonia Carosi, Department of Pathology, Istituto Nazionale Tumori "Regina Elena", Via Elio Chianesi 53, 00144 Rome, Italy
  • Andrea Salmaggi, Department of Neuro-oncology, Fondazione IRCCS Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy
  • Marta Maschio, Center for Brain Tumor-related Epilepsy, Istituto Nazionale Tumori "Regina Elena", Via Elio Chianesi 53, 00144 Rome, Italy

• Journal Journal of Neuro-Oncology
• Online ISSN 1573-7373
• Print ISSN 0167-594X

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