O6-Methylguanine-DNA-methyltransferase in recurring anaplastic ependymomas: PCR and immunohistochemistry.
Ependymomas are the third most common brain tumor in children. The post surgical management is controversial. There are no convincing data on an effective role for chemotherapy. O(6)-Methylguanine-DNA-Methyltransferase (MGMT) is a DNA repair protein considered to be a chemosensitivity predictor. Hypermethylation of the MGMT gene promoter is an important cause of MGMT inactivation. We evaluated the MGMT gene promoter methylation and the immunohistochemical MGMT protein expression in 12 recurrent anaplastic ependymomas affecting children. Our purpose was to investigate the molecular rationale of the administration of alkylating agents to children affected by recurrent anaplastic ependymomas. All ependymomas lacked MGMT promoter hypermethylation and 9 (75%) showed high MGMT protein expression (>50% tumoral cells). Differences between different recurrences in the same patient were not observed. These results may indicate MGMT as a factor of chemoresistance to alkylating drugs in anaplastic ependymomas and support the uncertainties regarding the actual benefit of chemotherapy for patients with anaplastic ependymomas.
Buccoliero
A M
AM
Department of Human Pathology and Oncology, University of Florence, Florence, Italy. ambuccoliero@unifi.it
Castiglione
F
F
Rossi Degl'Innocenti
D
D
Paglierani
M
M
Maio
V
V
Gheri
C F
CF
Garbini
F
F
Moncini
D
D
Taddei
A
A
Sardi
I
I
Sanzo
M
M
Giordano
F
F
Mussa
F
F
Genitori
L
L
Taddei
G L
GL
D000293:Adolescent; D000708:Anaplasia; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000096:biosynthesis* / Q000235:genetics; D045643:DNA Repair Enzymes / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D004806:Ependymoma / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes