IMMUNOHISTOCHEMICAL EXPRESSION OF P-GLYCOPROTEIN AND GLUTATHIONE S-TRANSFERASES IN CEREBRAL GLIOMAS AND RESPONSE TO CHEMOTHERAPY

The expression of the drug resistance-related proteins glutathione S-t ransferases (GST) and P-glycoprotein (Pgp) was analyzed quantitatively in samples of 53 astrocytic gliomas (eight WHO grade 1, 11 WHO grade 2, 9 WHO grade 3 and 25 glioblastomas, WHO grade 4). Sections of these tumors were immunohistochemically stained with antibodies to Pgp (MDR 1-gene product) and to GST subclasses alpha, mu and pi. Pgp expression was not detected in tumor cells of the majority of low-grade astrocyt omas (69%) and the percentage of Pgp stained cells generally increased with tumor grade. However, 4 of the 34 malignant gliomas were negativ e. Many neoplastic cells of most tumors were dominantly stained for GS T-pi. The other two subclasses were expressed in a less consistent fas hion with no linear correlation to grading. Grade 2 astrocytomas exhib ited the highest percentage of cells with GST expression. GST-alpha wa s absent in 9 tumors, GST-mu in 8 and GST-pi in 4. Four tumors showed no expression of any GST subclass or Pgp in neoplastic cells. Of 13 pa tients 5 with a more favorable clinical course after radiation and che motherapy had a lower percentage of neoplastic cells immunostained for Pgp and the three GST subclasses than 8 patients with a worse clinica l course. These results suggest a relationship between expression of d rug resistance-related proteins in gliomas and response to chemotherap y with ACNU/VM26.