Prognostic significance of glutathione S-transferase pi expression and subcellular localization in human gliomas

Abstract

The glutathione S-transferase (GST)-pi gene is overexpressed in many human cancers and preneoplastic lesions and is associated with failure of cancer chemotherapy and poor patient survival. Although GST-pi overexpression in tumors of the central nervous system has been observed, the prognostic and/or clinical relevance of this overexpression has, to date, not been investigated. In this study, we analyzed the level of GST-pi expression and its subcellular localization in 61 primary gliomas and correlated the results with tumor histology, patient age, and patient survival. We observed a strong positive correlation between the level of GST-pi expression and tumor grade and between the presence of GST-pi in glioma cell nuclei and patient age. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves showed the level of GST-pi expression and its nuclear localization to be inversely correlated with patient survival. Relative risk for death of patients with high versus low tumor GST-pi expression was 3.2 (P = 0.0069) by univariate analysis and 2.6 (P = 0.036) by multivariate analysis. The relative risk of death associated with the presence of nuclear GST-pi in glioma cells was 3.9 (P = 0.0001) by univariate analysis and 4.4 (P < 0.0001) by multivariate analysis. These data indicate that high GST-pi expression in tumor cells and the presence of the GST-pi protein in tumor cell nuclei are associated with clinically more aggressive gliomas and are strong predictors of poor patient survival.