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Evaluation status and prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in pediatric high grade gliomas

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Abstract

Introduction

In this study, we investigated the prognostic and predictive value of MGMT promoter methylation and protein expression in 30 pediatric high grade gliomas (pHGG).

Methods

MGMT promoter methylation was assayed by methylation-specific polymerase chain reaction (MSP), whereas MGMT protein expression was evaluated by immunohistochemistry (IHC).

Results

MGMT promoter methylation was observed in 7/24 (30%) cases, whereas MGMT protein overexpression was found in 19/28 (68%) cases with similar distribution in grade III and grade IV gliomas. Median survival of methylated and unmethylated patients was 16 and 8 months, respectively. Moreover, overall survival and progression-free survival showed a trend toward reduction in patients with unmethylation (p = 0.9 and p = 0.7, respectively). For MGMT protein expression, the median survival was 8.5 and 17 months for patients with MGMT overexpression or low expression, respectively. Although these two groups did not show statistically significant differences in terms of overall survival or progression-free survival (p = 0.8 and p = 0.7, respectively), there was a significant correlation between MGMT protein expression and MGMT promoter methylation status (p = 0.01).

Conclusions

Our findings indicate that, in pHGG, (a) MGMT promoter methylation is less frequent than in adult malignant gliomas, (b) there is a high correlation between MGMT MSP and MGMT IHC, and (c) as in adults, MGMT status is associated with prognosis, although this observation has to be statistically validated on larger series of patients.

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Acknowledgments

This study was in part supported by “Associazione Italiana per la Ricerca sul Cancro AIRC” and “Il Fondo di Giò Onlus”. Manila Antonelli is supported by a grant from Associazione Italiana per la Lotta al Neuroblastoma. We thank Maria Luisa Garrè for assistance with the clinical information and Alessandra Angiolosanto for technical assistance.

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Authors and Affiliations

  1. Department of Neurological Sciences, Sapienza University of Rome, Rome, Italy

    Francesca R. Buttarelli

  2. Pediatric Unit, IRCCS Istituto Nazionale Tumori, Milan, Italy

    Maura Massimino

  3. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Manila Antonelli

  4. Department of Anatomic Pathology, Università Cattolica del Sacro Cuore, Rome, Italy

    Libero Lauriola

  5. Department of Anatomic Pathology, Istituto G. Gaslini Ospedale Pediatrico IRCCS, Genoa, Italy

    Paolo Nozza

  6. Neurosurgery Institute, Università Cattolica del Sacro Cuore, Rome, Italy

    Concezio Di Rocco

  7. IRCCS Neuromed, Pozzilli, Isernia, Italy

    Antonella Arcella, Maria A. Oliva & Felice Giangaspero

  8. Department of Pathology, Ospedale Pausilipon AORN Santobono-Pausilipon, Naples, Italy

    Vittoria Donofrio

  9. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    Felice Giangaspero

  10. Neuropatologia c/o Neurochirurgia, Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy

    Felice Giangaspero

Authors
  1. Francesca R. Buttarelli
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  2. Maura Massimino
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  3. Manila Antonelli
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  4. Libero Lauriola
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  5. Paolo Nozza
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  6. Vittoria Donofrio
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  7. Antonella Arcella
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  8. Maria A. Oliva
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  9. Concezio Di Rocco
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  10. Felice Giangaspero
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Corresponding author

Correspondence to Felice Giangaspero.

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Buttarelli, F.R., Massimino, M., Antonelli, M. et al. Evaluation status and prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in pediatric high grade gliomas. Childs Nerv Syst 26, 1051–1056 (2010). https://doi.org/10.1007/s00381-010-1191-1

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  • DOI: https://doi.org/10.1007/s00381-010-1191-1

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