Breslow Norman E, Norris Robin, Norkool Patricia A, Kang Tammy, Beckwith J Bruce, Perlman Elizabeth J, Ritchey Michael L, Green Daniel M, Nichols Kim E
Department of Biostatistics, Box 357232, University of Washington, Seattle, WA 98195-7232, USA.
J Clin Oncol. 2003 Dec 15;21(24):4579-85. doi: 10.1200/JCO.2003.06.096.
Children with the rare Wilms tumor (WT)-aniridia (WAGR) syndrome have not had systematic evaluation of their clinical and pathologic features. We compared demographics, disease characteristics, and treatment outcomes in a large cohort of WT patients who did or did not have the WAGR syndrome.
Clinical and pathology records were reviewed for 8,533 patients enrolled between 1969 and 2002 by the National Wilms Tumor Study Group.
Sixty-four patients (0.75%) had the WAGR syndrome. For WAGR and non-WAGR patients, respectively, the average birth weights (2.94 and 3.45 kg), median ages at diagnosis (22 and 39 months), and the percentages with bilateral disease (17% and 6%), metastatic disease (2% and 13%), favorable histology (FH) tumors (100% and 92%), and intralobar nephrogenic rests (ILNR; 77% and 22%) all differed. Survival estimates for WAGR and non-WAGR patients were 95% +/- 3% and 92% +/- 0.3% at 4 years but 48% +/- 17% and 86% +/- 1.0%, respectively, at 27 years from diagnosis. Five late deaths in WAGR patients were from end-stage renal disease (ESRD).
The excess of bilateral disease, ILNR-associated FH tumors of mixed cell type, and early ages at diagnosis in WAGR patients all fit the known phenotypic spectrum of constitutional deletion of chromosome 11p13. Despite a favorable response of their WT to treatment, WAGR patients have a high risk of ESRD as they approach adulthood. The renal pathology associated with this apparent late manifestation of WT1 deletion, and the explanation for the abnormally low birth weights in patients with del 11p13, have yet to be determined.
患有罕见的肾母细胞瘤（WT）-无虹膜（WAGR）综合征的儿童尚未对其临床和病理特征进行系统评估。我们比较了一大群患有或未患有WAGR综合征的WT患者的人口统计学、疾病特征和治疗结果。
回顾了1969年至2002年间由国家肾母细胞瘤研究组登记的8533例患者的临床和病理记录。
64例患者（0.75%）患有WAGR综合征。WAGR患者和非WAGR患者的平均出生体重分别为（2.94和3.45千克）、诊断时的中位年龄（22和39个月）、双侧疾病的百分比（17%和6%）、转移性疾病的百分比（2%和13%）、预后良好组织学（FH）肿瘤的百分比（100%和92%）以及叶内肾源性残留（ILNR；77%和22%）均有所不同。WAGR患者和非WAGR患者在4年时的生存估计分别为95%±3%和92%±0.3%，但从诊断起27年时分别为48%±17%和86%±1.0%。WAGR患者中有5例晚期死亡是由于终末期肾病（ESRD）。
WAGR患者双侧疾病过多、与ILNR相关的混合细胞型FH肿瘤以及诊断时年龄较小，均符合已知的11p13染色体结构缺失的表型谱。尽管他们的WT对治疗反应良好，但WAGR患者在接近成年时患ESRD的风险很高。与WT1缺失这种明显晚期表现相关的肾脏病理学，以及11p13缺失患者出生体重异常低的原因，尚未确定。
