O6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry as a predictor of resistance to temozolomide in primary CNS lymphoma

Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) repairs alkylating damage, such as that induced by temozolomide. We hypothesized that MGMT immunohistochemistry would predict r...

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Bibliographic Details
Published in:Journal of neuro-oncology 2013-08, Vol.114 (1), p.135-140
Main Authors: Jiang, Xiaoyin, Reardon, David A., Desjardins, Annick, Vredenburgh, James J., Quinn, Jennifer A., Austin, Alan D., Herndon, James E., McLendon, Roger E., Friedman, Henry S.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Alkylating - adverse effects
Central Nervous System Neoplasms - drug therapy
Central Nervous System Neoplasms - metabolism
Clinical Study
Dacarbazine - adverse effects
Dacarbazine - analogs & derivatives
Drug Resistance, Neoplasm
Female
Humans
Longitudinal Studies
Lymphoma - drug therapy
Lymphoma - metabolism
Male
Medicine
Medicine & Public Health
Middle Aged
Neurology
O-Methylguanine-DNA Methyltransferase - metabolism
Oncology
Retrospective Studies
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Summary:Temozolomide, an alkylating agent, has shown promise in treating primary central nervous system lymphoma (PCNSL). The enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) repairs alkylating damage, such as that induced by temozolomide. We hypothesized that MGMT immunohistochemistry would predict resistance to temozolomide in PCNSL. A retrospective study of newly-diagnosed and recurrent PCNSL patients treated at our institution was conducted to study the predictive value of MGMT immunohistochemistry for response to temozolomide. 20 patients who were treated with temozolomide as a single agent were identified during the study time period. 6/20 patients demonstrated a response, corresponding to an objective response rate of 30 % (95 % CI 8–52). Five patients with low MGMT level (
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-013-1162-y