Glutathione S-transferases and cytochrome P450 detoxifying enzyme distribution in human cerebral glioma

Abstract

Malignant astrocytomas are frequently resistant to cytotoxic chemotherapy. A possible mechanism of chemoresistance is drug inactivation within malignant astrocytes by detoxifying enzymes (glutathione transferases (GST) and cytochrome P450's). The aim of this study was to assess whether there was differential expression of these detoxifying enzymes in the central nervous system and any relationship to histological grade (WHO) of the tumours. Immunostaining was performed in 30 consecutive glioma samples, using class specific polyclonal antibodies to subtypes of GST (pi, alpha, mu) and to human cytochrome P450 reductase. GST immunostaining was evident in astrocytes and endothelium but not neurones or oligodendrocytes in normal brain. Immunostaining for GST increased in intensity from well differentiated tumours to glioblastoma. Staining was least evident in surrounding normal brain, strong in reactive astrocytes and astrocytic tumour cells and very intense in gemistocytic and giant tumour cells. Small anaplastic tumour cells had very little GST staining. Where endothelial proliferation was evident, GST staining in endothelial cells was increased. Pi was always the predominant subclass, although GST alpha and mu were also expressed in some tumours. Cytochrome P450 reductase immunostaining was present in normal neurones and malignant astrocytes. Gemistocytic astrocytic tumour cells stained intensely. Further work is necessary to see if there is any correlation between immunostaining intensity survival or response to chemotherapy.