Correlation between promoter hypermethylation of the O6-methylguanine-deoxyribonucleic acid methyltransferase gene and prognosis in patients with high-grade astrocytic tumors treated with surgery, radiotherapy, and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea-based chemotherapy.
OBJECTIVE
O(6)-Methylguanine-deoxyribonucleic acid methyltransferase (MGMT) is a deoxyribonucleic acid repair protein associated with the chemoresistance of chloroethylnitrosoureas. We investigated whether MGMT promoter hypermethylation is associated with prognosis in patients with high-grade astrocytic tumors treated uniformly with surgery, radiotherapy, and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-based chemotherapy.


METHODS
Using the methylation-specific polymerase chain reaction, we assayed promoter hypermethylation of the MGMT gene in tumor deoxyribonucleic acid from 116 adult patients with supratentorial high-grade astrocytic tumors (42 anaplastic astrocytomas [AAs] and 74 glioblastomas multiforme [GBMs]). The Cox proportional hazards model was used in forward stepwise regression to assess the relative role of prognostic factors (i.e., age at surgery, sex, Karnofsky Performance Scale score, extent of surgical resection, methylation status of the MGMT promoter, and association between MGMT promoter methylation and survival).


RESULTS
MGMT promoter hypermethylation was confirmed in 19 (45.2%) of 42 AA patients and 33 (44.6%) of 74 GBM patients. It was significantly associated with both longer overall and progression-free survival time in AA but not GBM patients.


CONCLUSIONS
Our results demonstrate that MGMT promoter hypermethylation is associated with longer survival time in patients with AA who were treated with surgery, radiotherapy, and ACNU-based chemotherapy but not in patients with GBM.
Kamiryo
Takanori
T
Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan. tkamiryo-nsu@umin.ac.jp
Tada
Kenji
K
Shiraishi
Shoji
S
Shinojima
Naoki
N
Kochi
Masato
M
Ushio
Yukitaka
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D019175:DNA Methylation; D005260:Female; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000627:therapeutic use; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012189:Retrospective Studies
D000970:Antineoplastic Agents; D015376:Nimustine; D019853:O(6)-Methylguanine-DNA Methyltransferase