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Tumour and serum MGMT promoter methylation and protein expression in glioblastoma patients

Clinical and Translational Oncology volume 13, Article number: 677 (2011) Cite this article

Abstract

Introduction

Methylation of the promoter of the MGMT gene and MGMT protein expression are recognized as predictive markers for response to alkylating chemotherapy in glioblastoma (GB).

Material and methods

We have assessed MGMT methylation with the methylation-specific polymerase chain reaction (MSP) in tumor samples from 70 GB patients and in serum samples from 37 of these patients. We have also assessed MGMT protein expression by immunohistochemical (IHC) analysis in tissue samples from 63 of these patients.

Results

We found concordance between MGMT methylation status in tissue and serum (Cohen’s Kappa = 0.586; p<0.0001). MSP for detection of non-methylated MGMT promoter in serum showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation test showed a low specificity (8.9%). Patients whose MGMT promoter was methylated in tissue attained longer progression-free and overall survival. In the multivariate analysis, serum MGMT promoter methylation emerged as an independent factor for longer progression-free and overall survival.

Conclusion

Serum-based MGMT methylation analysis offers a promising alternative to tumor-based MGMT analysis in cases where tissue samples are unavailable.

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Affiliations

  1. Medical Oncology Service Catalan Institute of Oncology (ICO) Hospital Germans Trias i Pujol, Ctra. Canyet, s/n, ES-08916, Badalona, Barcelona, Spain

    Carmen Balañá, José Luis Ramírez, Andrés Felipe Cardona, Mireia Berdiel, Miquel Tarón & Rafael Rosell

  2. Department of Pathology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

    Cristina Carrato, Eva Musulen & Aurelio Ariza

  3. Clinical and Translational Oncology Group, Institute of Oncology Fundación Santa Fe de Bogotá, Bogotá, Colombia

    Andrés Felipe Cardona

  4. Biostatistics and Clinical Research Unit, Universidad Autónoma de Madrid, Madrid, Spain

    José Javier Sánchez

  5. Neurosurgery Service, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain

    Cristina Hostalot

Authors
  1. Carmen Balañá
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  2. Cristina Carrato
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  3. José Luis Ramírez
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  7. Miquel Tarón
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  11. Rafael Rosell
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Correspondence to Carmen Balañá.

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Balañá, C., Carrato, C., Ramírez, J.L. et al. Tumour and serum MGMT promoter methylation and protein expression in glioblastoma patients. Clin Transl Oncol 13, 677 (2011). https://doi.org/10.1007/s12094-011-0714-x

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  • DOI: https://doi.org/10.1007/s12094-011-0714-x

Keywords

  • O 6-methylguanine-DNA-methyltransferase (MGMT)
  • Methylation-specific polymerase chain reaction (MSP)
  • Immunohistochemistry
  • Serum
  • Tissue
  • Glioblastoma
  • Survival
  • Concordance