Oligodendrogliomas lacking O6-methylguanine-DNA-methyltransferase expression.
O6-Methylguanine-DNA-Methyltransferase (MGMT) is a DNA repair protein considered to be a chemosensitivity predictor. We evaluated the immunohistochemical MGMT expression in 28 consecutive oligodendroglial tumors (21 oligodendrogliomas, 5 mixed oligoastrocytomas, and 2 glioblastomas with prominent oligodendroglial features; 13 treated with CCNU) and compared it with that of 13 glioblastomas. Twenty-six (93%) oligodendroglial tumors were MGMT-negative, 2 (7%) were MGMT-positive. Twelve (92%) patients treated with CCNU had MGMT-negative lesions and their median survival was 73 months; 1 patient had an MGMT-positive oligodendroglioma and is alive at 28 months. Three (23%) glioblastomas were MGMT-negative and 10 (77%) MGMT-positive. The lower MGMT expression in oligodendroglial tumors compared to glioblastomas (P < 0.05), which have different chemosensitivity, suggests a possible role of MGMT in the determination of chemoresistance. Nevertheless, the heterogeneous outcome of our MGMT-negative oligodendroglial tumors treated with CCNU, indicates that MGMT expression alone is insufficient to predict the response to alkylating drugs, presumably because of the numerous mechanisms involved.
Buccoliero
A M
AM
Department of Human Pathology and Oncology, University of Florence, Italy. ambuccoliero@unifi.it
Arganini
L
L
Ammannati
F
F
Gallina
P
P
Di Lorenzo
N
N
Mennonna
P
P
Taddei
G L
GL
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000032:analysis* / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D019853:O(6)-Methylguanine-DNA Methyltransferase