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Departments of Pediatric Urology [M. A. G., M. H. A. O., M. A. N., R. M. N., G. J. V. S.] and Pathology [T. H. V. d. K., J. C. D. H.], Josephine Nefkens Institute, and The Netherlands Institute for Health Sciences [M. K. S.], Erasmus University, 3000 DR Rotterdam, the Netherlands; Department of Pediatric Oncology, University Hospital, 3015 GD Rotterdam, the Netherlands [M. M. V. d. H.]; and Urology Department, Menoufiya University, Shebin El-Kom, Egypt [S. M. N.]
ABSTRACT
Wilms tumor is one of the most common solid tumors of children. The protein product of the tumor-suppressor gene, Wilms tumor 1 (WT-1), binds to the same DNA sequences as the protein product of the early growth response 1 (EGR-1) gene. There is experimental evidence that EGR-1 is involved in controlling cell growth. The expression of both genes in Wilms tumor was studied by others, mainly at the mRNA level. The present study evaluates the prognostic value of WT-1 and EGR-1 in 61 Wilms tumors of chemotherapeutically treated patients at the protein level, using an immunohistochemical approach. WT-1 was expressed in normal kidney tissues and in the blastemal and epithelial component of Wilms tumor, whereas stromal tissue was negative. EGR-1 was expressed in normal kidney tissues and in the three main cell types of Wilms tumor. In 59 and 56% of Wilms tumor, the blastemal cells stained for WT-1 and EGR-1, respectively. The blastemal expression of WT-1 and EGR-1 and the epithelial expression of WT-1 were statistically significantly correlated with clinical stage. WT-1 immunoreactivity correlated with EGR-1 expression. Univariate analysis showed that blastemal WT-1 and EGR-1 expression were indicative for clinical progression and tumor-specific survival, whereas epithelial staining was of no prognostic value. Multivariate analysis showed that blastemal WT-1 expression is an independent prognostic marker for clinical progression other than stage. We conclude that a relationship exists between WT-1 and EGR-1 expression in clinical nephroblastomas. Blastemal WT-1 and EGR-1 expression is related to prognosis.
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