Topoisomerase II alpha in Wilms tumors: gene alterations and immunoexpression

¹ University of Chicago, United States
² Van Andel Research Institute, United States
³ Northwestern University, United States

^* To whom correspondence should be addressed. E-mail: xyang{at}northwestern.edu.

Accepted 24 November 2005

	Abstract

Background: Topoisomerase II alpha (TopoII), an essential enzyme encoded by TOP2A gene in regulating DNA structure and cell proliferation. TOP2A has been reported as one of the top genes overexpressed in Wilms tumor (WT) by using cDNA microarray analysis.

Aims/Methods: In order to evaluate the role of TopoII in WT tumorigenesis and its prognostic value, we studied TOP2A gene copy numbers by FISH and TopoII protein expression levels by immunostaining in 39 primary and 18 metastatic WT samples.

Results: TOP2A gene amplification was detected only in anaplastic WT, whereas none of WT showed deletion of TOP2A gene. The TopoII protein overexpression was detected in 97% of WT, and correlated strongly with proliferation, as measured by Ki67 (r=0.85). The high TopoII expression was associated with presence of vascular invasion, prominent apoptosis, metastases and adverse clinical outcomes (p<0.05).

Conclusions: Our findings suggest that TopoII overexpression in Wilms tumors is caused by a change at the transcription level except for anaplastic WT where gene amplification was present. Our findings show that high levels of TopoII protein are correlated with tumor aggressiveness and assessment of TopoII expression in WT may have prognostic value.

Key Words: FISH, Topoisomerase II, Wilms tumor, immunohistochemistry, prognosis

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