Topoisomerase IIalpha in Wilms' tumour: gene alterations and immunoexpression.
BACKGROUND
Topoisomerase IIalpha (topoIIalpha) 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.


OBJECTIVE
To evaluate the role of TopoIIalpha 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 TopoIIalpha 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. TopoIIalpha protein overexpression was detected in 97% of Wilms' tumours, and correlated strongly with proliferation, as measured by Ki-67 (r = 0.85). The high TopoIIalpha expression was associated with the presence of vascular invasion, prominent apoptosis, metastases and adverse clinical outcomes (p<0.05).


CONCLUSIONS
Our findings suggest that TopoIIalpha 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 TopoIIalpha protein are correlated with tumour aggressiveness. The assessment of TopoIIalpha expression in Wilms' tumour may have prognostic value.
Department of Pathology, University of Chicago, Chicago, Illinois 60611, USA.
M
M
Tretiakova
M
M
Turkyilmaz
T
T
Grushko
M
M
Kocherginsky
C
C
Rubin
B
B
Teh
X J
XJ
Yang
D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D016019:Survival Analysis; D009396:Wilms Tumor / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000556:secondary
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human