BIOLOGIC PROGNOSTIC VARIABLES IN WILMS TUMOR PATIENTS

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Modern treatment methods have led to major improvements in survival rates of children with Wilms' tumor. Multimodality therapy including nephrectomy and chemotherapy results in long-term survival of 90% of children with stage I and II favorable histology Wilms' tumor while treatment with nephrectomy, radiation therapy and three-drug chemotherapy with vincristine, actinomycin D and doxorubicin results in long-term relapse-free survival of 85 % of patients with stage III and IV, favorable histology Wilms' tumor. Clinical and pathological features have not allowed accurate identification of those patients destined to relapse within each stage. This identification is necessary to allow administration of more aggressive treatment regimens to the small group of patients who are destined to relapse without exposing those patients with an excellent prognosis using current treatment methods to the additional risk associated with more aggressive chemotherapeutic regimens. Biological variables have been identified and prospectively evaluated in children with other malignancies and have been found to aid in the identification of children at greater risk of recurrence of their disease. We propose to evaluate 250-300 children with Wilms' tumor to determine if (1) loss of heterozygosity for chromosomal regions 11p13, 11p15, 16q or 1p, (2) duplication of chromosome region 1q and/or (3) absent expression of the WT1 gene predicts significantly worse two-year relapse-free survival in children with Wilms' tumor; (4) to determine whether Wilms' tumors which contain a mutation at one or both alleles of WT1 gene are associated with a clinically worse prognosis; (5) to determine whether nuclear morphometric characteristics can be identified which accurately discriminate patients with favorable histology tumors who have an adverse prognosis with currently available treatment methods. The results of this research may allow more accurate identification of Wilms' tumor patients whose prognosis is poor with current therapeutic methods. More aggressive therapy may then be evaluated in this group of patients in the future to determine if such therapy improves the prognosis for these patients.