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

Francesca R. Buttarelli, Maura Massimino, Manila Antonelli, Libero Lauriola, Paolo Nozza, Vittoria Donofrio, Antonella Arcella, Maria A. Oliva, Concezio Di Rocco, Felice Giangaspero

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1051-1056
Number of pages6
JournalChild's Nervous System
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Methyltransferases
Glioma
Methylation
Pediatrics
DNA
Protein Methyltransferases
Survival
O-(6)-methylguanine
Disease-Free Survival
Immunohistochemistry

Keywords

  • Expression
  • Methylation
  • MGMT
  • Pediatric glioma
  • Survival

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Evaluation status and prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in pediatric high grade gliomas. / Buttarelli, Francesca R.; Massimino, Maura; Antonelli, Manila; Lauriola, Libero; Nozza, Paolo; Donofrio, Vittoria; Arcella, Antonella; Oliva, Maria A.; Di Rocco, Concezio; Giangaspero, Felice.

In: Child's Nervous System, Vol. 26, No. 8, 08.2010, p. 1051-1056.

Research output: Contribution to journalArticle

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AU - Massimino, Maura

AU - Antonelli, Manila

AU - Lauriola, Libero

AU - Nozza, Paolo

AU - Donofrio, Vittoria

AU - Arcella, Antonella

AU - Oliva, Maria A.

AU - Di Rocco, Concezio

AU - Giangaspero, Felice

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N2 - 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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