Differential expression of the drug resistance markers DNA topoisomerase II alpha and glutathione S-transferase-pi in the histological compartments of Wilms' tumors

More than 80 % of the patients presenting with Wilms' tumor can be cured to day. Some patients, however, fail to respond to chemotherapy. The objective of this study was to analyze the immunohistochemical distribution of two m arkers of cytostatic drug resistance, e.g. DNA topoisomerase II alpha (Topo II alpha) and glutathione S-transferase-pi (GST-pi) in 23 Wilms' tumor pat ients who had undergone an operation between 1984 and 1997. Eight patients had stage I disease, seven stage II; three stage III, four stage IV, and on e stage V disease. Five tumors showed high malignancy histology. Investigat ions were carried out on formalin-fixed and paraffin-embedded tissue sectio ns using the indirect immunoperoxidase method. Topo II alpha was predominan tly present in the epithelial components of the specimens. It was more freq uently found in anaplastic tumors. There was no difference in the presence of Topo II alpha in the epithelial components between specimens derived fro m treated and untreated patients. Topo II alpha was however; less expressed in the blastemal and stromal elements of specimens after preoperative trea tment If GST-pi was present, it was confined to the epithelial components e xcept for one case. While no expression of GST-pi was found in preoperative ly untreated Wilms' tumors, it was present in epithelial compartments in 57 % of tumors after chemotherapy. In conclusion, preoperative chemotherapy l ed to compartment-specific alterations in the expression levels of both mar kers indicating a contribution to treatment response of Wilms' tumors.