Prognostic implications of gain of 1q in favorable histology Wilms tumor: A report from the Children’s Oncology Group.

Abstract

10014 Background: Wilms tumor is the most common childhood renal tumor. While the majority of patients with favorable histology Wilms Tumor (FHWT) have good outcomes, many patients still experience recurrence and death from disease. This study’s goal was to determine if chromosome 1q gain is associated with event-free (EFS) and overall survival (OS) in FHWT. Methods: Unilateral FHWT samples were obtained from patients enrolled on National Wilms Tumor Study-4 and Pediatric Oncology Group 9046, “A Molecular Genetic analysis of Wilms Tumor.” 1q gain, 1p loss, and 16q loss were determined using multiplex ligation-dependent probe amplification (MLPA). Results: The eight-year EFS was 87% (95% CI 82%, 91%) for the entire cohort of 212 patients. Tumors of 58/212 patients (27%) displayed 1q gain. A strong relationship between 1q gain and 1p/16q loss was observed. The eight-year EFS was 76% (95% CI 63%, 85%) for those with 1q gain and 93% (95% CI 87%, 96%) for those lacking 1q gain (p=0.0024). The eight-year OS was 89% (95% CI 78%, 95%) for those with 1q gain, and 98% (95% CI 94%, 99%) for those lacking 1q gain (p=0.0075). Gain of 1q did not correlate with disease stage (p=0.16). After stratification for stage, 1q gain was associated with a significant increase in the risk of failure (risk ratio estimate: 2.72, p=0.0089). Conclusions: Gain of 1q is associated with inferior EFS and OS in FHWT and may provide a new and valuable prognostic marker to stratify therapy for patients with FHWT. A confirmatory study is necessary before this biomarker is incorporated into risk stratification schema of future therapeutic studies.