BIOLOGIC PROGNOSTIC VARIABLES IN WILMS TUMOR PATIENTS

现代治疗方法已导致生存率的重大改善 患有肾母细胞瘤的儿童 综合治疗包括 肾切除术和化疗导致90%的患者长期存活， I期和II期组织学良好的肾母细胞瘤儿童， 肾切除、放疗和三药化疗 长春新碱、放线菌素D和多柔比星导致长期 85%的III期和IV期患者的无复发生存率， 组织学良好的肾母细胞瘤。 临床和病理特征 无法准确识别那些注定要 每个阶段的复发。 这种识别是必要的， 对小群体给予更积极的治疗方案 那些注定要复发的病人， 使用目前的治疗方法， 与更积极的化疗相关的额外风险 养生法 已经确定了生物学变量， 在患有其他恶性肿瘤的儿童中进行了评估， 在确定儿童的复发风险更大， 疾病 我们建议评估250-300例肾母细胞瘤患儿， 确定是否（1）染色体区域11 p13的杂合性丢失， 11 p15、16 q或1 p，（2）染色体区域1 q的重复和/或（3） WT 1基因的缺失表达预示着2年内 肾母细胞瘤儿童的无复发生存率;（4）确定 是否在一个或两个等位基因上含有突变的肾母细胞瘤 WT 1基因与临床预后不良有关; 确定是否可以识别核形态学特征 其准确地区分具有良好组织学肿瘤的患者 目前可用的治疗方法预后不良的患者。 这项研究的结果可以更准确地识别 目前治疗预后差的肾母细胞瘤患者 方法. 然后可以在这组患者中评估更积极的治疗。 患者在未来，以确定这种治疗是否改善 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.