MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities.
MGMT promoter methylation, which has been correlated with the response to alkylating agents, was investigated in a retrospective series of 219 glioblastomas (GBMs) treated with various modalities. MGMT methylation had no impact on survival for the whole group, but showed a significant advantage (17.1 months vs. 13.1) for patients treated with RT+ adjuvant chemotherapy (relative risk of death (RR) = 0.53; P = 0.041), particularly when patients received CT during the course of RT (MS = 19.9 months vs. 12.5 months; RR = 0.227, P = 0.001). This suggests that the prognostic impact of MGMT methylation is dependent on therapeutic modalities and schedules. MGMT methylation was not correlated with the main molecular alterations, such as 10q loss and p53 expression.
Crinière
Emmanuelle
E
INSERM, U711, Biologie des Interactions Neurones & Glie, Université Pierre et Marie Curie, Faculté de Médecine, Paris, France.
Kaloshi
Gentian
G
Laigle-Donadey
Florence
F
Lejeune
Julie
J
Auger
Nathalie
N
Benouaich-Amiel
Alexandra
A
Everhard
Sibille
S
Mokhtari
Karima
K
Polivka
Marc
M
Delattre
Jean-Yves
JY
Hoang-Xuan
Khê
K
Thillet
Joëlle
J
Sanson
Marc
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D066298:In Vitro Techniques; D008745:Methylation; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes