Prognostic significance of glutathione S-transferase pi expression and subcellular localization in human gliomas.
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.
Ali-Osman
F
F
Section of Molecular Therapeutics, Department of Experimental Pediatrics, Division of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
Brunner
J M
JM
Kutluk
T M
TM
Hess
K
K
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005909:Glioblastoma / Q000201:enzymology / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005910:Glioma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005982:Glutathione Transferase / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D015388:Organelles / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D011379:Prognosis; D013347:Subcellular Fractions / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D016019:Survival Analysis
D007527:Isoenzymes; D005982:Glutathione Transferase