Gene expression analysis and the risk of relapse in favorable histology Wilms' tumor.

Abstract

Introduction and objectives: Wilms' tumor (WT) relapse occurs in 15% of patients. We aim to investigate the association between the expression of several genetic markers and WT relapse risk.

Materials and methods: The study included 51 children treated for WT at a tertiary center between 2001 and 2019: 23 patients had disease relapse (group A) and 28 remained relapse-free after at least 2 years of follow-up (group B). Patients with syndromic, bilateral synchronous or anaplastic WT were excluded. Autologous renal tissue from 20 patients served as control. Total RNA was isolated from tumor tissue and control. Gene expression levels of WT1, HIF1α, b-FGF, c-MYC and SLC22A18 were assessed using quantitative RT-PCR and normalized to GAPDH. Immunohistochemical staining for WT1 and gene expression levels were compared between the study groups.

Results: Median patient age was 3 (IQR = 2-5) years and 36 (70.6%) had stage I disease. Baseline characteristics were similar between study groups. Relapse occurred at a median of 6.8 (2.8-24.7) months, predominantly in the lungs (11/23, 47.8%). Tumors that relapsed expressed significantly higher levels of WT1, HIF1α, b-FGF and c-MYC and lower levels of SLC22A18 (p < 0.001). Strong immunohistochemical staining for WT1 was seen in 73.9% of group A and 14.29% of group B (p < 0.001). These associations retained statistical significance irrespective of patient and tumor characteristics.

Conclusions: Higher expression levels of WT1, HIF1 α, b-FGF and c-MYC and lower level of SLC22A18 are associated with increased risk of WT relapse. These genetic markers can serve as future prognostic predictors and help stratify patients for treatment.