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Topoisomerase II in Wilms’ tumour: gene alterations and immunoexpression

¹ Department of Pathology, University of Chicago, Chicago, Illinois, USA
² Department of Hematology and Oncology, University of Chicago
³ Department of Health Studies, University of Chicago
⁴ Department of Pediatrics, University of Chicago
⁵ Van Andel Research Institute, Grand Rapids, Michigan, USA
⁶ Department of Pathology, Northwestern Memorial Hospital, Northwestern University, Feinberg School of Medicine, Chicago

Correspondence to:
X J Yang
Department of Pathology, Feinberg 7-334, Northwestern Memorial Hospital, Northwestern University, Feinberg School of Medicine, 251 E Huron Street, Chicago, IL 60611,USA; xyang{at}northwestern.edu Background: Topoisomerase II (topoII) is an essential enzyme gene in regulating DNA structure and cell proliferation and is encoded by the TOP2A. Using cDNA microarray analysis, TOP2A has been reported to be one of the top genes overexpressed in Wilms’ tumour.

Aim: To evaluate the role of TopoII in Wilms’ tumorigenesis and its prognostic value.

Methods: TOP2A gene copy numbers were determined using the fluorescence in situ hybridisation technique, and protein expression levels of TopoII by immunostaining in 39 samples of primary and 18 samples of metastatic Wilms’ tumour.

Results: TOP2A gene amplification was detected only in anaplastic Wilms’ tumours, and none of the Wilms’ tumours showed deletion of the TOP2A gene. TopoII protein overexpression was detected in 97% of Wilms’ tumours, and correlated strongly with proliferation, as measured by Ki-67 (r = 0.85). The high TopoII expression was associated with the presence of vascular invasion, prominent apoptosis, metastases and adverse clinical outcomes (p<0.05).

Conclusions: Our findings suggest that TopoII overexpression in Wilms’ tumours is caused by a change at the transcription level, except for anaplastic Wilms’ tumours, in which gene amplification was present. High levels of TopoII protein are correlated with tumour aggressiveness. The assessment of TopoII expression in Wilms’ tumour may have prognostic value.

Abbreviations: FISH, fluorescence in situ hybridisation; IHC, immunohistochemistry; PFS, progression-free survival; TMA, tissue microarray; topoII, topoisomerase II

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