Relationship between expression of O⁶-methylguanine-DNA methyltransferase, glutathione-S-transferase in glioblastoma and the survival of the patients treated with nimustine hydrochloride: An immunohistochemical analysis

Authors: Anda T.¹; Shabani H.K.²; Tsunoda K.²; Tokunaga Y.²; Kaminogo M.²; Shibata S.³; Hayashi T.⁴; Iseki M.⁵

Source: Neurological Research, Volume 25, Number 3, April 2003 , pp. 241-248(8)

Publisher: Maney Publishing

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Abstract:

Drug resistance is one of the important factors that determine tumor response to chemotherapy. Several candidates for resistance to various chemotherapeutic agents have been elucidated. O⁶-methylguanineDNA methyltransferase (MGMT) removes methylation damage induced by nitrosourea from the O⁶ position of DNA guanines before cell injury. Glutathione-S-transferase (GST)

is also involved in nitrosourea resistance. We examined the expression of MGMT and GST

in 18 glioblastomas (GBM) using immunohistochemistry and compared the results with patients' survival after administration of 1-(4- amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-based chemotherapy. According to the Kaplan-Meier's method, although median progression free survival (PFS) of eight patients whose tumors retained high MGMT (3 +~ 2 + ), and 10 patients whose tumors showed low MGMT expression (1 +~ 0) were nine and 15 months, respectively ( p= 0.09), median overall survival (OS) of the two groups were 12 and 22 months, respectively, which were significantly different ( p= 0.01). GST

expression in GBM was not a prognostic factor. It is suggested that GBM with strong staining of MGMT activity may show more resistance to ACNU-based chemotherapy compared to that with low MGMT. The simple immunohistochemical analysis of MGMT in GBM can be a useful method to determine whether ACNU or another treatment regimen should be recommended.

Keywords: GLIOBLASTOMA; DRUG RESISTANCE; MGMT; NIMUSTINE

Document Type: Research article

DOI: 10.1179/016164103101201445

Affiliations: 1: Department of Neurosurgery, Nagasaki University School of Medicine, map Department of Neurosurgery, National Nagasaki Medical Center, Nagasaki, Japan Department of Neurosurgery, National Nagasaki Medical Center, Nagasaki, Japan "> 2: Department of Neurosurgery, Nagasaki University School of Medicine, Nagasaki, Japan 3: Department of Neurosurgery, Nagasaki University School of Medicine, Nagasaki & Department of Neurosurgery, Miyazaki Hospital, Miyazaki, Japan 4: Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan 5: Department of Pathology, Institute of Tropical Medicine Nagasaki University, Nagasaki, Japan

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