Expression of resistance‐related proteins in nephroblastoma after chemotherapy

Abstract Tumor tissues of untreated and cytostatic‐agent‐treated patients with nephroblastomas were investigated for expression of resistance‐related proteins (P‐glycoprotein, glutathione S‐transferase‐π, glutathione peroxidase and topoisomerase II) to ascertain whether resistance proteins are changed after treatment. Tumor tissue was analyzed by means of mRNA. Twenty‐three children were treated with actinomycin D and vincristine for 4 to 8 weeks. Eight children received no pre‐operative chemotherapy. In untreated patients, no expression of P‐glycoprotein was seen, whereas, in the patients who were treated with actinomycin D and vincristine, 12 out of 23 tumors showed increased P‐glycoprotein expression (> mean value). Although we found no difference between treated and untreated tumors for glutathione S‐transferase‐π, we found significant 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 content. With treatment, 11 tumors expressed low levels and 12 tumors high levels of mRNA. A significant positive correlation between P‐glycoprotein and glutathione peroxidase was found. In addition, of the 8 untreated patients, 2 had low topoisomerase‐ll expression, and 6 high expression. With treatment, the expression was reduced in 18 tumors, and only 5 tumors had high levels of this protein. These results were confirmed by PCR and immunohistochemistry.