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-transferases (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 (MDR1-gene product) and to GST subclasses alpha, mu and pi. Pgp expression was not detected in tumor cells of the majority of low-grade astrocytomas (69%) and the percentage of Pgp stained cells generally increased with tumor grade. However, 4 of the 34 malignant gliomas were negative. Many neoplastic cells of most tumors were dominantly stained for GST-pi. The other two subclasses were expressed in a less consistent fashion with no linear correlation to grading. Grade 2 astrocytomas exhibited the highest percentage of cells with GST expression. GST-alpha was 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 patients 5 with a more favorable clinical course after radiation and chemotherapy had a lower percentage of neoplastic cells immunostained for Pgp and the three GST subclasses than 8 patients with a worse clinical course. These results suggest a relationship between expression of drug resistance-related proteins in gliomas and response to chemotherapy with ACNU/VM26.
von Bossanyi
P
P
Department of Neuropathology, Magdeburg University Medical School, Germany.
Diete
S
S
Dietzmann
K
K
Warich-Kirches
M
M
Kirches
E
E
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001254:Astrocytoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D017567:Karnofsky Performance Status; D015376:Nimustine / Q000008:administration & dosage; D013713:Teniposide / Q000008:administration & dosage
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007527:Isoenzymes; D015376:Nimustine; D013713:Teniposide; D005982:Glutathione Transferase