Amplification and expression of EGFR and ERBB2 in Wilms tumor.
Wilms tumor is one of the most common solid tumors in children. We evaluated expression and amplification of a number of genes and their prognostic significance in 45 patients with Wilms tumor, using tissue microarray technology. The expression of EGFR, ERBB2, MDM2, CCND1, MLH1, MSH2, TP53, and ABCB1 (alias MDR1) was studied by immunohistochemistry. Amplification of the EGFR, ERBB2, MDM2, CCND1, CTTN (previously EMS1), RAF1, MYC, FGF3 (previously INT2), WNT1, GLI1, CDK4, and NCOA3 (alias AIB1) genes was assessed by fluorescence in situ hybridization. Expression of EGFR was seen in 17 of the 45 cases (38%) but was not associated with gene amplification. The ERBB2 gene was neither overexpressed nor amplified in any case. Tissue microarray and immunohistochemistry analyses for ERBB2 in whole-tumor sections were also negative in all cases. Strong p53 reactivity was noted in blastemal cells in two cases with an unfavorable outcome. ABCB1 reactivity was seen in five cases with favorable histology and outcome. Only one case showed nuclear cyclin D1 positivity. All tumors showed MLH1 and MSH2 expression. All examined genes showed normal copy numbers. Unfavorable histology correlated with poor prognosis (P=0.03). There was no significant association between gene expression and prognosis. Overexpression of the EGFR gene in many Wilms tumor cases warrants further study to determine the therapeutic benefit of EGFR inhibitors in combination with other therapies in Wilms tumor patients.
Department of Pathology, Shiraz Medical School and Shiraz Institute of Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran. vaseim@sums.ac.ir
Mohammad
M
Vasei
Helmout
H
Modjtahedi
Oreineb
O
Ale-Booyeh
Ahmad
A
Mosallaei
Abdol Mohammad
AM
Kajbafzadeh
Mehdi
M
Shahriari
Abbas Ali
AA
Ghaderi
Hossein
H
Soleymanpour
Farid
F
Kosari
Holger
H
Moch
Guido
G
Sauter
D000293:Adolescent; D000818:Animals; D002648:Child; D002675:Child, Preschool; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D014183:Transplantation, Heterologous; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human