p53 expression in Wilms' tumor: a possible role as prognostic factor.

Although a correlation between anaplasia and mutations of the p53 tumor suppressor gene has been found in Wilms' tumor (WT) a prognostic significance of p53 in WT remains largely unresolved. The goal of this study was to obtain a better understanding of the role of p53 expression in WT. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded tumor tissues from 21 patients treated in our clinic between 1984 and 1996. Eight patients presented with stage I, six with stage II, two with stage III, four with stage IV and one patient with stage V disease. According to the presence of anaplasia, four cases were categorized as of unfavorable histology based on the criteria of the National Wilms' Tumor Study Group. Seven out of 21 WTs were positive for p53. One out of the eight patients with stage I and one out of the six patients with stage II disease scored positive for p53 as were 2/2 patients with stage III and 3/4 patients with stage IV disease. Four tumors scored positive for anaplasia (one stage I, one stage II and two stage IV disease) and all four belonged to the p53 positive group. Three of these patients died of progressive disease. Immunopositivity in general was focal in the blastemal and epithelial parts of the tumors, with differences in intensity of staining ranging from moderate to strong. Positivity in the stromal components was restricted to single cells. Statistical analysis revealed significant correlations of p53 expression to anaplasia and to survival, respectively. The association of p53 expression to tumor stage was of borderline significance. To support immunohistochemistry, we performed PCR/SSCP and DNA sequence analyses on two cases, one whose immunopositivity suggested a mutated p53, and another case which was immunonegative. A CGG --> TGG base change in codon 282 of exon 8 was found in the immunopositive tumor. In conclusion, p53 may be of prognostic relevance for poor outcome being present in close association with unfavorable histology of WTs.