Evaluation status and prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in pediatric high grade gliomas.
BACKGROUND
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.
Buttarelli
Francesca R
FR
Department of Neurological Sciences, Sapienza University of Rome, Rome, Italy.
Massimino
Maura
M
Antonelli
Manila
M
Lauriola
Libero
L
Nozza
Paolo
P
Donofrio
Vittoria
V
Arcella
Antonella
A
Oliva
Maria A
MA
Di Rocco
Concezio
C
Giangaspero
Felice
F
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000096:biosynthesis / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes