Relationship between expression of O6-methylguanine-DNA methyltransferase, glutathione-S-transferase pi in glioblastoma and the survival of the patients treated with nimustine hydrochloride: an immunohistochemical analysis.
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-methylguanine-DNA methyltransferase (MGMT) removes methylation damage induced by nitrosourea from the O6 position of DNA guanines before cell injury. Glutathione-S-transferase (GST) pi is also involved in nitrosourea resistance. We examined the expression of MGMT and GST pi 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+ approximately 2+), and 10 patients whose tumors showed low MGMT expression (1+ approximately 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 pi 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.
Department of Neurosurgery, Nagasaki University School of Medicine, National Nagasaki Medical Center, Nagasaki. anda@nmc.hosp.go.jp
Takeo
T
Anda
Hamisi Kimaro
HK
Shabani
Keishi
K
Tsunoda
Yoshiharu
Y
Tokunaga
Makio
M
Kaminogo
Shobu
S
Shibata
Tomayoshi
T
Hayashi
Masachika
M
Iseki
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000627:therapeutic use; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis* / Q000276:immunology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007527:Isoenzymes; D015376:Nimustine; D019853:O(6)-Methylguanine-DNA Methyltransferase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase