BIOLOGIC PROGNOSTIC VARIABLES IN WILMS TUMOR PATIENTS

现代治疗方法极大地提高了存活率 患有肾母细胞瘤的儿童。综合治疗包括 肾切除和化疗可使90%的患者长期存活 组织学I、II期儿童肾母细胞瘤 肾切除、放射治疗和三联化疗的治疗 与长春新碱、放线菌素D和阿霉素联合使用可导致长期 85%的III和IV期患者无复发生存， 组织学良好的肾母细胞瘤。临床和病理特点 不允许准确识别那些注定要 在每个阶段都会复发。此身份识别是必要的，以允许 对小群体实施更积极的治疗方案 在不暴露这些患者的情况下注定会复发的患者 在目前的治疗方法下预后良好的 与更积极的化疗相关的额外风险 养生法。已经确定了生物变量，并展望了 在患有其他恶性肿瘤的儿童中进行评估，并被发现有助于 在确定儿童有更大的复发风险时， 疾病。我们建议评估250-300名患有肾母细胞瘤的儿童 确定是否(1)染色体区域11p13的杂合性丢失， 11p15、16q或1p，(2)染色体区域1q和/或(3)的重复 WT1基因表达缺失预示着两年内病情显著恶化 儿童肾母细胞瘤的无复发生存率；(4)确定 无论Wilms‘s肿瘤是否包含一个或两个等位基因突变 WT1基因与临床预后较差有关；(5) 确定是否可以识别核形态计量学特征 准确区分具有良好组织学肿瘤的患者 目前可用的治疗方法对预后不利。 这项研究的结果可能会使更准确地识别 目前治疗预后不良的肾母细胞瘤患者 方法：研究方法。然后在这一组患者中评估更积极的治疗方法 以确定这种疗法是否能改善患者的 这些患者的预后。

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.