Expression and prognostic value of Wilms' tumor 1 and early growth response 1 proteins in nephroblastoma

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.