EXPRESSION OF RESISTANCE-RELATED PROTEINS IN NEPHROBLASTOMA AFTER CHEMOTHERAPY

Tumor tissues of untreated and cytostatic-agent-treated patients with nephroblastomas were investigated for expression of resistance-related proteins (P-glycoprotein, glutathione S-transferase-pi, glutathione p eroxidase and topoisomerase II) to ascertain whether resistance protei ns are changed after treatment. Tumor tissue was analyzed by means of mRNA. Twenty-three children were treated with actinomycin D and vincri stine for 4 to 8 weeks. Eight children received no preoperative chemot herapy. In untreated patients, no expression of P-glycoprotein was see n, whereas, in the patients who were treated with actinomycin D and vi ncristine, 12 out of 23 tumors showed increased p-glycoprotein express ion (> mean value). Although we found no difference between treated an d untreated tumors for glutathione S-transferase-pi, we found signific ant differences in the expression of glutathione peroxidase. In the 8 untreated patients, 7 tumors showed low glutathione peroxidase (< mean value) and one high (> mean value) glutathione-peroxidase-mRNA conten t. With treatment, II tumors expressed low levels and 12 tumors high l evels of mRNA. A significant positive correlation between P-glycoprote in and glutathione peroxidase was found. In addition, of the 8 untreat ed patients, 2 had low topoisomerase-II expression, and 6 high express ion. With treatment, the expression was reduced in 18 tumors, and only 5 tumors had high levels of this protein. These results were confirme d by PCR and immunohistochemistry. (C) 1995 Wiley-Liss, Inc.