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

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