IMMUNOHISTOCHEMICAL DETECTION OF P53 IN WILMS-TUMORS CORRELATES WITH UNFAVORABLE OUTCOME

The role of p53 in the pathogenesis and progression of Wilms' tumors i s only partly understood. Although p53 mutations were initially report ed only in anaplastic Wilms' tumors, we had reported that, of two of t wenty-one cases that had a p53 mutation, one tumor showed no evidence of anaplasia. To determine the significance of p53 expression in all c linical stages of Wilms' tumor, twenty-eight cases were analyzed for p 53 immunoreactivity, Paraffin sections were immunolabeled with two dif ferent monoclonal antibodies, recognizing both mutant and wild-type p5 3, Fifteen of sixteen tumors in the recurrent/metastatic group and thr ee of twelve tumors 112 the nonmetastatic/nonrecurrent group showed p5 3 immunopositivity. Only one of three positive tumors in the latter gr oup showed moderate to strong positivity, whereas twelve of sixteen me tastatic/recurrent tumors revealed a similar degree of p53 positivity. The positivity was stronger in the metastasis/recurrences as compared with the corresponding primary tumor. Western blot analysis revealed p53 expression in all of the Wilms' tumors tested, suggesting its invo lvement in the development of Wilms' tumors. Single-strand conformatio n polymorphism analysis performed on twenty-three of these tumors reve aled p53 mutations in four of fourteen recurrent/metastatic tumors and none ill the nonmetastatic/nonrecurrent group. Our results show that, whereas 60% of cases were immunopositive for p53 protein, mutations w ere detected in only 16% of tumors, indicating that wild-type p53 prot ein is retained in the other tumors, We conclude that p53 immunopositi vity strongly correlates with recurrence/metastasis in Wilms' tumors. Furthermore, the accumulation of p53 ill these tumors is not only due to mutations brit may also involve stabilization of normal p53 with ot her proteins.