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 today. Some patients, however, fail to respond to chemotherapy. The objective of this study was to analyze the immunohistochemical distribution of two markers of cytostatic drug resistance, e.g. DNA topoisomerase II alpha (Topo II alpha) and glutathione S-transferase-pi (GST-pi) in 23 Wilms' tumor patients 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 one stage V disease. Five tumors showed high malignancy histology. Investigations were carried out on formalin-fixed and paraffin-embedded tissue sections using the indirect immunoperoxidase method. Topo II alpha was predominantly present in the epithelial components of the specimens. It was more frequently found in anaplastic tumors. There was no difference in the presence of Topo II alpha in the epithelial components between specimens derived from treated and untreated patients. Topo II alpha was, however, less expressed in the blastemal and stromal elements of specimens after preoperative treatment. If GST-pi was present, it was confined to the epithelial components except for one case. While no expression of GST-pi was found in preoperatively untreated Wilms' tumors, it was present in epithelial compartments in 57% of tumors after chemotherapy. In conclusion, preoperative chemotherapy led to compartment-specific alterations in the expression levels of both markers indicating a contribution to treatment response of Wilms' tumors.
Granzen
B
B
Department of Children and Adolescents, University Hospital Aachen, Germany.
Efferth
T
T
Keller
U
U
Beniers
A J
AJ
Mertens
R
R
Jakse
G
G
Füzesi
L
L
D000951:Antigens, Neoplasm; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007223:Infant; D007527:Isoenzymes / Q000032:analysis*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery / Q000648:ultrastructure; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000201:enzymology; D009392:Nephrectomy; D011292:Premedication; D017154:Stromal Cells / Q000201:enzymology; D009396:Wilms Tumor / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; D005982:Glutathione Transferase; D004250:DNA Topoisomerases, Type II