Wilms' Tumour
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Wilms' Tumour

Wilms' tumour is a cancer of the kidney which is very different to adult kidney cancer. Most patients are under 5 years of age at diagnosis, though Wilms' tumour is sometimes seen in older children and occasionally in young adults. In most cases only one kidney has disease (unilateral-Wilms' Tumour); but in some cases both kidneys are affected (bilateral-Wilms' tumour). A small minority of cases are known to be hereditary. Other less common kidney cancers in children include malignant rhabdoid tumours and clear cell sarcoma. Treatment for these is usually similar to that for Wilms' tumour.

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    MeSH term: Wilms Tumor
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Liu Z, He F, OuYang S, et al.
miR-140-5p could suppress tumor proliferation and progression by targeting TGFBRI/SMAD2/3 and IGF-1R/AKT signaling pathways in Wilms' tumor.
BMC Cancer. 2019; 19(1):405 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Wilms' tumor is also called nephroblastoma and is the most common pediatric renal cancer. Several genetic and epigenetic factors have been found to account for the development of Wilms' tumor. MiRNAs play important roles in this tumorigenic process. In the present study, we aimed to investigate the role of miR-140-5p in nephroblastoma by identifying its targets, as well as its underlying molecular mechanism of action.
METHODS: The miRNA expression profile of nephroblastoma samples was investigated and the targets of miR-140-5p were predicted and validated using the miRNA luciferase reporter method. Moreover, the roles of miR-140-5p in regulating nephroblastoma cell proliferation, migration and cell cycle were analyzed by the CCK8, migration and flow cytometry assays, respectively. The downstream protein of the direct target of miR-140-5p was also identified.
RESULTS: miR-140-5p was downregulated in Wilms' tumor tissues, whereas in the nephroblastoma cell lines G401 and WT-CLS1 that exhibited high levels of miRNA-140-5p, inhibition of cellular proliferation and metastasis were noted as well as cell cycle arrest at the G1/S phase. TGFBRI and IGF1R were identified as direct target genes for miRNA-140-5p. In addition, SMAD2/3 and p-AKT were regulated by TGFBRI and IGF1R separately and participated in the miRNA-140-5p regulatory network. Ectopic expression of TGFBR1 and IGF-1R could abrogate the inhibitory effect of miR-140-5p.
CONCLUSION: We demonstrated that miRNA-140-5p participates in the progression of Wilms' tumor by targeting the TGFBRI/SMAD2/3 and the IGF-1R/AKT signaling pathways.

Guntiboina VA, Islam N, Banerjee S, Chatterjee U
Post therapy Wilms tumour or ectopic immature renal tissue: A pathologist's diagnostic dilemma.
Indian J Pathol Microbiol. 2019 Apr-Jun; 62(2):266-269 [PubMed] Related Publications
Post chemotherapy Wilms Tumour (PCWT) is a diagnostic conundrum both for the clinician and the pathologist, in view of its morphological similarity with ectopic immature renal tissue (EIRT). However, due to their varying prognoses and different lines of management, it is important to distinguish between the two. Here, we discuss clinical presentation and pathology of a case of PCWT, arising in a horse shoe deformity of the kidney in a 5 year old girl. The discussion focuses on the pathogenesis of Extra Renal Wilms Tumour (ERWT) as well as its distinguishing morphological features and chemotherapy induced changes in Wilms tumour.

Phelps HM, Pierce JM, Murphy AJ, et al.
FXR1 expression domain in Wilms tumor.
J Pediatr Surg. 2019; 54(6):1198-1205 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
BACKGROUND/PURPOSE: Wilms tumor (WT) is the most common childhood kidney cancer globally. Our prior unbiased proteomic screen of WT disparities revealed increased expression of Fragile X-Related 1 (FXR1) in Kenyan specimens where survival is dismal. FXR1 is an RNA-binding protein that associates with poor outcomes in multiple adult cancers. The aim of this study therefore was to validate and characterize the FXR1 expression domain in WT.
METHODS: Quantitative FXR1 gene expression was compared between WT, adjacent, adult, and fetal kidney specimens. The cellular and subcellular expression domain of FXR1 was characterized across these tissues using immunoperoxidase staining. RNA-sequencing of FXR1 was performed from WT and other pediatric malignancies to examine its broader target potential.
RESULTS: FXR1 was detected in all clinical WT specimens evaluated (n = 82), and as a result appeared independent of demographic, histology, or adverse event. Specific cytosolic staining was strongest in blastema, intermediate and variable in epithelia, and weakest in stroma. When present, areas of skeletal muscle differentiation stained strongly for FXR1. qPCR revealed increased FXR1 expression in WT compared to adult and adjacent kidney (p < 0.0002) but was similar to fetal kidney (p = 0.648). RNA-sequencing revealed expression of FXR1 in multiple pediatric tumors, greatest in rhabdomyosarcoma and WT.
CONCLUSIONS: FXR1 was expressed consistently across this broad sampling of WT and most robustly in the primitive blastema. Notably, FXR1 labeled a specific self-renewing progenitor population of the fetal kidney.

Manzoor R, Yasmeen N
Upfront Nephrectomy Versus Preoperative Chemotherapy In Wilm's Tumour.
J Ayub Med Coll Abbottabad. 2019 Jan-Mar; 31(1):104-107 [PubMed] Related Publications
BACKGROUND: Wilms tumour is the most common renal tumour in paediatric age group. This study was done to compare the two approaches used for treatment, namely upfront nephrectomy versus pre-operative chemotherapy..
METHODS: A descriptive cross-sectional study was done enrolling all the patients of Wilms tumour reporting to Oncology unit Children's Hospital during the study period. A total of 80 patients were divided into 2 groups. One group (n=40) had upfront surgery while the other (n=40) received pre-op chemotherapy before surgery. Both groups were compared for outcomes including whether treatment completed and declared cured, lost during treatment against medical advice, or died during treatment.
RESULTS: It was found that stage 2 patients were more likely to get upfront surgery done while stage 3, 4 and 5 were likely to get pre-operative chemotherapy before nephrectomy. Also, favourable histology was associated with better outcome overall outcome.

Sapio MR, Iadarola MJ, LaPaglia DM, et al.
Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity.
Pain. 2019; 160(5):1070-1081 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (BDNF) gene, a crucial trophic factor for nociceptive afferents. Nociceptive responses assessed by quantitative sensory testing demonstrated reduced pain sensitivity only in the WAGR subjects whose deletion boundaries included the BDNF gene. Corresponding behavioral assessments were made in heterozygous Bdnf knockout rats to examine the specific role of Bdnf. These analogous experiments revealed impairment of Aδ- and C-fiber-mediated heat nociception, determined by acute nociceptive thermal stimuli, and in aversive behaviors evoked when the rats were placed on a hot plate. Similar results were obtained for C-fiber-mediated cold responses and cold avoidance on a cold-plate device. Together, these results suggested a blunted responsiveness to aversive stimuli. Our parallel observations in humans and rats show that hemizygous deletion of the BDNF gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.

Jia W, Deng F, Fu W, et al.
Curcumin suppresses wilms' tumor metastasis by inhibiting RECK methylation.
Biomed Pharmacother. 2019; 111:1204-1212 [PubMed] Related Publications
Wilms' tumor (WT) is the most common kidney tumor of children. The transformation suppressor gene RECK, which codes membrane-anchored glycoprotein, frequently downregulates multiple matrix metalloproteinases in tumors. And curcumin, which is a polyphenlic compound separated from turmeric, has antitumor effects on various cancers. However, the correlation of WT, RECK and curcumin is still unrevealed. In this study, we evaluated that the methylation degree of RECK was much higher in WT than in adjacent non-tumor tissues. And RECK methylation was closely associated with tumor metastasis in WT patients. After curcumin treatment, the level of RECK methylation was decreased significantly. And the expression of MMP2 and MMP9 was reduced consequently. Moreover, the proliferation, invasion and migration ability of WT cells were suppressed after curcumin treatment. Meanwhile, the apoptosis rate of WT cells was increased simultaneously. In nude mice model, curcumin restrained ability of tumorigenicity and promoted apoptosis of WT cells. Together, our results suggest that the RECK methylation can serve as a prognostic biomarker of WT. Moreover, curcumin could inhibit RECK methylation, thereby abates the expression of MMPs, and suppresses the tumor progression and metastasis of WT.

Ni D, Liu J, Hu Y, et al.
A1CF-Axin2 signal axis regulates apoptosis and migration in Wilms tumor-derived cells through Wnt/β-catenin pathway.
In Vitro Cell Dev Biol Anim. 2019; 55(4):252-259 [PubMed] Related Publications
A1CF, a complementary factor of APOBEC-1, is involved in many cellular processes for its mRNA editing role, such as cell proliferation, apoptosis, and migration. Here, we explored the regulatory function of A1CF in Wilms tumor-derived cells. Quantitative real-time PCR was performed to detect the mRNA level of A1CF, Axin2, β-Catenin, CCND1 or NKD1 in A1CF-depleted or A1CF-overexpression G401 cells. Western bolt was used to analyze the expression of A1CF, Axin2, and β-catenin protein. The cell apoptosis and migration ability were determined using flow cytometry assay or wound healing, respectively. Our study demonstrated that overexpression of A1CF, Axin2 was upregulated and knockdown of A1CF decreased Axin2 expression at mRNA and protein levels in G401 cells. Besides, knockdown of A1CF further upregulated β-catenin, the classical regulator of Wnt signal pathway, and increased CCND1 and NKD1, the target genes of Wnt/β-catenin. Furthermore, overexpression of Axin2 partly rescued the expression of β-catenin in A1CF-deficiency stable G401 cells. In Wnt agonist BML-284 treated G401 cells, A1CF was increased like other classical regulator of Wnt signal pathway, such as Axin2 and β-catenin. Meanwhile, knockdown of Axin2 rescued β-catenin expression which was decreased in A1CF overexpression condition with BML-284. Further, overexpression of A1CF reduced cell apoptosis but promoted cell migration, and overexpression of Axin2 got similar results. In A1CF-decreased stable G401 cells, overexpression of Axin2 partly rescued the cell apoptosis and migration. We find that A1CF is a positive regulator of Axin2, a Wnt/β-catenin pathway inhibitor, and A1CF-Axin2 signal axis regulates Wilms tumor-derived cells' apoptosis and migration through Axin2.

Li H, Huang D, Hang S
Salidroside inhibits the growth, migration and invasion of Wilms' tumor cells through down-regulation of miR-891b.
Life Sci. 2019; 222:60-68 [PubMed] Related Publications
AIMS: Salidroside is a major functional component of Rhodiola rosea L. with a lot of pharmacological effects, including anti-tumor. The present work aimed to explore whether Salidroside could also exhibit anti-tumor functions in Wilms' tumor.
MAIN METHODS: WIT49 and RM1 cells were treated by various doses of Salidroside. CCK-8 assay, flow cytometry detection, colony formation assay, Transwell assay, RT-qPCR and Western blot analysis were conducted to measure WIT49 and RM1 cells proliferation, apoptosis, migration and invasion. The expression changes of miR-891b in response to Salidroside treatment were tested by RT-qPCR. Rescue assays were performed to test whether miR-891b was a downstream effector of Salidroside. Finally, the involvement of PI3K/AKT/mTOR and NF-κB signaling pathways was studied.
KEY FINDINGS: Salidroside with concentration of 80 μM significantly reduced WIT49 and RM1 cells viability, survival capacity, migration and invasion, and significantly induced apoptosis. Meanwhile, down-regulation of Cyclin D1, MMP-2 and Vimentin, up-regulations of p53 and p21, as well as cleavage of caspase-3 and -9 were observed in Salidroside-treated cell. miR-891b was down-regulated by Salidroside. And Salidroside did not suppress WIT49 and RM1 cells growth, migration and invasion when miR-891b was overexpressed. Also, the deactivation of PI3K/AKT/mTOR and NF-κB pathways induced by Salidroside was reversed by miR-891b overexpression.
SIGNIFICANCE: Salidroside inhibits Wilms' tumor cells growth, migration and invasion via down-regulating miR-891b, which leads to the deactivation of PI3K/AKT/mTOR and NF-κB signaling pathways.

Liu K, He B, Xu J, et al.
miR-483-5p Targets MKNK1 to Suppress Wilms' Tumor Cell Proliferation and Apoptosis In Vitro and In Vivo.
Med Sci Monit. 2019; 25:1459-1468 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
BACKGROUND Wilms' tumor (WT) is the most common type of renal tumor in children and it has high mortality rates. MicroRNAs (miRNAs) are important regulators of cellular differentiation processes that have been discovered to contribute to the development of various kinds of tumors. MATERIAL AND METHODS The Wilms' tumor tissues and adjacent tissues were obtained from 28 patients to quantity miR-483-5p expression level. The miR-483-5p mimics and scrambles were transfected into the human kidney WT cell line GHINK-1 to evaluate the effect of miR-483-5p on Wilms' tumor cell proliferation and apoptosis in vitro. A total of 18 female BALB/c nu/nu mice were used to further confirm how miR-483-5p affects Wilms' tumor in vivo. RESULTS In the present study, miR-483-5p was identified to be downregulated in Wilms' tumor tissues compared with the normal adjacent tissues. Additionally, low expression of mir-483-5p was significantly correlated with unfavorable histology subtypes, lymphatic metastasis, and late clinical stage (stage III and IV). Overexpression of miR-483-5p inhibited the proliferation and colony formation of GHINK-1 (Wilms' tumor) cells compared with the control group due to enhanced cell apoptosis. Furthermore, miR-483-5p upregulated the protein expression level of caspase-3. Finally, MAP kinase-interacting serine/threonine-protein kinase 1 was identified as a direct target of miR-483-5p, which was confirmed by luciferase reporter assay and Western blotting. CONCLUSIONS miR-483-5p suppressed WT cell proliferation via inducing apoptosis through targeting MKNK1. This may provide novel insights into the mechanisms underlying WT and a potential therapeutic candidate for the treatment of WT in the future.

Koshinaga T, Takimoto T, Okita H, et al.
Blastemal predominant type Wilms tumor in Japan: Japan Children's Cancer Group.
Pediatr Int. 2019; 61(4):351-357 [PubMed] Related Publications
BACKGROUND: Persistence of blastemal components after chemotherapy is a marker of poor outcome in Wilms tumor (WT). Recent reports from local Japanese areas have described pre-chemotherapy blastemal predominant type WT to also be a risk factor for relapse. The significance, however, of blastemal predominant WT remains to be evaluated in a larger study. This study retrospectively evaluated the prognostic significance of pre-chemotherapy blastemal predominant type WT in the Japan Wilms tumor Study (JWiTS) trials.
METHODS: The JWiTS trial (1996-2013) was a prospective, single-arm study. The outcomes of blastemal predominant type WT were retrospectively evaluated compared with non-blastemal type WT excluding anaplasia between 1996 and 2013. Relapse-free survival (RFS) and overall survival (OS) were estimated.
RESULTS: Of 319 primary renal tumors diagnosed by the central pathology review system, advanced stage of pre-chemotherapy blastemal predominant type WT (n = 53; 16.1%) occurred more frequently in older children than non-blastemal type WT (n = 225), and was especially frequent in female patients registered in the JWiTS trials. No significant difference in 10 years RFS and OS (78.8% vs 84.5; P = 0.201) or in 10 years RFS and OS (89.3% vs 93.5; P = 0.45) was seen between pre-chemotherapy blastemal predominant type and non-blastemal type WT.
CONCLUSIONS: Relapse-free survival and OS are not significantly different between pre-chemotherapy blastemal predominant type and non-blastemal type WT.

Probst PJ, Assadi A, Gleason J
Botryoid Wilms Tumor: A Rare Diagnosis With an Atypical Presentation.
Urology. 2019; 126:192-194 [PubMed] Related Publications
Wilms tumor commonly presents as an asymptomatic abdominal mass. In some cases, it can be accompanied with hypertension, constitutional symptoms, and hematuria when involving the collecting system. Below, we review the case of a child diagnosed with botryoid Wilms tumor involving the upper calyces and renal pelvis in which the presenting symptom was a concern for a foreign body in her left ear, and the only abnormality during initial history and physical examination was stage II hypertension.

Rossoff J, Tse WT, Duerst RE, et al.
High-dose chemotherapy and autologous hematopoietic stem-cell rescue for treatment of relapsed and refractory Wilms tumor: Re-evaluating outcomes.
Pediatr Hematol Oncol. 2018 Aug - Sep; 35(5-6):316-321 [PubMed] Related Publications
Wilms tumor (WT) treatment regimens are curative for more than 80% of patients, but those with relapsed or refractory disease continue to have poor outcomes. High-dose chemotherapy followed by autologous stem cell rescue is often utilized although outcomes remain variable. We report on HD-ASCR outcomes in 24 patients with relapsed or refractory Wilms tumor. Three-year disease free and overall survival are 46% and 60%, respectively, which is similar to those reported for conventional salvage therapies. These outcomes suggest that conventional salvage therapies should be employed for relapsed and refractory WT rather than HD-ASCR.

Wang X, Song P, Huang C, et al.
Weighted gene co‑expression network analysis for identifying hub genes in association with prognosis in Wilms tumor.
Mol Med Rep. 2019; 19(3):2041-2050 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
Wilms tumor (WT) is the most common type of renal malignancy in children. Survival rates are low and high‑risk WT generally still carries a poor prognosis. To better elucidate the pathogenesis and tumorigenic pathways of high‑risk WT, the present study presents an integrated analysis of RNA expression profiles of high‑risk WT to identify predictive molecular biomarkers, for the improvement of therapeutic decision‑making. mRNA sequence data from high‑risk WT and adjacent normal samples were downloaded from The Cancer Genome Atlas to screen for differentially expressed genes (DEGs) using R software. From 132 Wilms tumor samples and six normal samples, 2,089 downregulated and 941 upregulated DEGs were identified. In order to identify hub DEGs that regulate target genes, weighted gene co‑expression network analysis (WGCNA) was used to identify 11 free‑scale gene co‑expressed clusters. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were annotated using KEGG Orthology Based Annotation System annotation of different module genes. The Search Tool for the Retrieval of Interacting Genes was used to construct a protein‑protein interaction network for the identified DEGs, and the hub genes of WGCNA modules were identified using the Cytohubb plugin with Cytoscape software. Survival analysis was subsequently performed to highlight hub genes with a clinical signature. The present results suggest that epidermal growth factor, cyclin dependent kinase 1, endothelin receptor type A, nerve growth factor receptor, opa‑interacting protein 5, NDC80 kinetochore complex component and cell division cycle associated 8 are essential to high‑risk WT pathogenesis, and they are closely associated with clinical prognosis.

Liu P, Zhuo Z, Li W, et al.
Biosci Rep. 2019; 39(1) [PubMed] Article available free on PMC after 01/06/2020 Related Publications
Wilms tumor is the most common renal malignancy that occurs in children.

Oostveen RM, Pritchard-Jones K
Pharmacotherapeutic Management of Wilms Tumor: An Update.
Paediatr Drugs. 2019; 21(1):1-13 [PubMed] Related Publications
Although differences exist in treatment and risk-stratification strategies for children with Wilms tumor (WT) between the European [International Society of Paediatric Oncology (SIOP)] and American [Children's Oncology Group (COG)] study groups, outcomes are very similar, with an overall survival of > 85%. Future strategies aim to de-intensify treatment and reduce toxicity for children with a low risk of relapse and intensify treatment for children with high-risk disease. For metastatic WT, response of lung nodules to chemotherapy is used as a marker to modify treatment intensity. For recurrent WT, a unified approach based on the use of agents that were not used for primary therapy is being introduced. Irinotecan is being explored as a new strategy in both metastatic and relapsed WT. Introduction of biology-driven approaches to risk stratification and new drug treatments has been slower in WT than in some other childhood cancers. While several new biological pathways have been identified recently in WT, their individual rarity has hampered their translation into clinical utility. Identification of robust prognostic factors requires extensive international collaborative studies because of the low proportion who relapse or die. Molecular profiling studies are in progress that should ultimately improve both risk classification and signposting to more targeted therapies for the small group for whom current therapies fail. Accrual of patients with WT to early-phase trials has been low, and the efficacy of these new agents has so far been very disappointing. Better in vitro model systems to test mechanistic dependence are needed so available new agents can be more rationally prioritized for recruitment of children with WT to early-phase trials.

Wang J, Lei W, Li G, et al.
CD151 promotes proliferation and migration of SK-NEP-1 cells via the GSK-3β/P21/cyclinD signaling pathway.
Pathol Res Pract. 2019; 215(2):329-334 [PubMed] Related Publications
Wilms'tumor is the most common malignant tumor with a poor clinical prognosis because of metastasis or recurrence among children worldwide. CD151, a member of transmembrane 4 superfamily, has now been confirmed to be involved in tumor progression including the proliferation, migration, invasion and metastasis of tumor cells. GSK-3β/P21/cyclinD signaling pathway plays a critical role in the cell cycle progression, regulating cellular proliferation. In this study, CD151 protein and mRNA levels were examined by western blot and RT-PCR. The proliferation of SK-NEP-1 cells was examined by CCK8 assay and the migration of SK-NEP-1 cells was detected with wound healing assay. Furthermore, p-GSK3β protein, GSK3β protein, p21protein and CyclinD protein were examined by western blot to verify whether CD151 could regulate the Wilms'tumor progression via the GSK-3β/P21/cyclinD signaling pathway. The RT-PCR and western blot results showed that CD151 protein was upregulated in Wilms'tumor cells compared with the control. The results by CCK8 assay and wound healing assay demonstrated that CD151 overexpression promoted the proliferation and migration in SK-NEP-1 cells and CD151 interference showed the opposite effects. Western blot assay revealed that CD151 activated the GSK-3β/P21/cyclinD signaling pathway and upregulated the expression of p-GSK3β protein, p21protein and CyclinD protein. It was also verified that CD151 promotes proliferation and migration of SK-NEP-1 cells through the GSK-3β/P21/cyclinD signaling pathway in this study. The specific aim of the study is to investigate and verify the role of CD151 in Wilm's tumor. Therefore, in-depth study on the molecular mechanisms will provide new strategies and methods for the treatment of Wilm's tumor.

Armstrong AE, Gadd S, Huff V, et al.
A unique subset of low-risk Wilms tumors is characterized by loss of function of TRIM28 (KAP1), a gene critical in early renal development: A Children's Oncology Group study.
PLoS One. 2018; 13(12):e0208936 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
This study explores the genomic alterations that contribute to the formation of a unique subset of low-risk, epithelial differentiated, favorable histology Wilms tumors (WT), tumors that have been characterized by their expression of post-induction renal developmental genes (Subset 1 WT). We demonstrate copy neutral loss of heterozygosity involving 19q13.32-q13.43, unaccompanied by evidence for imprinting by DNA methylation. We further identified loss-of-function somatic mutations in TRIM28 (also known as KAP1), located at 19q13, in 8/9 Subset 1 tumors analyzed. An additional germline TRIM28 mutation was identified in one patient. Retrospective evaluation of previously analyzed WT outside of Subset 1 identified an additional tumor with anaplasia and both TRIM28 and TP53 mutations. A major function of TRIM28 is the repression of endogenous retroviruses early in development. We depleted TRIM28 in HEK293 cells, which resulted in increased expression of endogenous retroviruses, a finding also demonstrated in TRIM28-mutant WT. TRIM28 has been shown by others to be active during early renal development, and to interact with WTX, another gene recurrently mutated in WT. Our findings suggest that inactivation of TRIM28 early in renal development contributes to the formation of this unique subset of FHWTs, although the precise manner in which TRIM28 impacts both normal renal development and oncogenesis remains elusive.

Guerreiro F, Seravalli E, Janssens GO, et al.
Potential benefit of MRI-guided IMRT for flank irradiation in pediatric patients with Wilms' tumor.
Acta Oncol. 2019; 58(2):243-250 [PubMed] Related Publications
PURPOSE/OBJECTIVE: Flank irradiation for Wilms' tumor (WT) is currently performed at our institute using a cone-beam computed tomography-guided volumetric modulated arc (VMAT
MATERIAL/METHODS: 4D-CT, MRI and CBCT scans acquired during preparation and treatment of 15 patients, were used to estimate both geometric, motion and patient set-up systematic (∑) and random (σ) errors for VMAT
RESULTS: Analysis of ∑ and σ errors resulted in a PTV
CONCLUSIONS: Imaging data in children with WT demonstrated that the PTV margin could be reduced isotropically down to 2 mm when using the IMRT

Su H, Wang X, Song J, et al.
MicroRNA-539 inhibits the progression of Wilms' Tumor through downregulation of JAG1 and Notch1/3.
Cancer Biomark. 2019; 24(1):125-133 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
BACKGROUND: Previous studies demonstrated that miR-539 play an important role in the carcinogenesis of some cancers. The aim of the present study was to determine the role of miR-539 in the pathogenesis of Wilms' Tumor (WT).
METHODS: The expression level of miR-539 was measured by qRT-PCR in 42 WT tissues and SK-NEP-1 cell line. Protein expression of genes (E-cadherin, N-cadherin, Vimentin, Notch 1, Notch 3 and JAG1) was assessed by Western blot. The function of miR-539 was investigated in SK-NEP-1 cells by MTT and Transwell assays. The relationship between miR-539 and JAG1 was verified by a dual luciferase assay in SK-NEP-1 cells.
RESULTS: The expression level of miR-539 was significantly decreased in WT tissues. Downregulation of miR-539 was closely related to NWTS-5 stage, lymph node metastasis and histological type of WT patients. Furthermore, low miR-539 expression was associated with a shorter overall survival rate in WT patients. In vitro, overexpression of miR-539 suppressed proliferation, migration and invasion of SK-NEP-1 cells. In addition, JAG1 was a direct target of miR-539. MiR-539 inhibited the development of WT by inhibiting JAG1-Notch1/3 expressing and blocking EMT.
CONCLUSION: MiR-539 inhibited the progression of WT through downregulation of JAG1 and Notch1/3.

Haruta M, Arai Y, Okita H, et al.
Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome.
Neoplasia. 2019; 21(1):117-131 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
To identify prognostic factors, array CGH (aCGH) patterns and mutations in WT1 and 9 other genes were analyzed in 128 unilateral Wilms tumors (WTs). Twenty patients had no aCGH aberrations, and 31 had WT1 alterations [silent and WT1 types: relapse-free survival (RFS), 95% and 83%, respectively]. Seventy-seven patients had aCGH changes without WT1 alterations (nonsilent/non-WT1 type) and were subtyped into those with or without +12, 11q-, 16q-, or HACE1 loss. RFS was better for those with than those without +12 (P = .010) and worse for those with than those without 11q-, 16q-, or HACE1 loss (P = .001, .025, or 1.2E-04, respectively). Silent and WT1 type and 8 subtype tumors were integrated and classified into 3 risk groups: low risk for the silent type and +12 subgroup; high risk for the no +12 plus 11q-, 16q-, or HACE1 loss subgroup; intermediate risk for the WT1 type and no +12 plus no 11q-, 16q-, or HACE1 loss subgroup. Among the 27 WTs examined, the expression of 146 genes on chromosome 12 was stronger in +12 tumors than in no +12 tumors, while that of 10 genes on 16q was weaker in 16q- tumors than in no 16q- tumors. Overexpression in 75 out of 146 upregulated genes and underexpression in 7 out of 10 downregulated genes correlated with better and worse overall survival, respectively, based on the public database. +12 was identified as a potential new marker predicting a favorable outcome, and chromosome abnormalities may be related to altered gene expression associated with these abnormalities.

Vujanić GM, Schiavo Lena M, Sebire NJ
Botryoid Wilms tumor: a non-existent "entity" causing diagnostic and staging difficulties.
Virchows Arch. 2019; 474(2):227-234 [PubMed] Related Publications
Wilms tumors growing in a botryoid fashion into the renal pelvis have been reported since the 1960s as a rare tumor type usually associated with stromal histology and a good prognosis. However, the true frequency, association with Wilms tumor subtypes, and stage have never been comprehensively studied. We analyzed all Wilms tumors enrolled into the International Society of Paediatric Oncology (SIOP) United Kingdom 2001 Trial (2001-2011), which showed botryoid growth. In addition, we reviewed published series reporting papers on botryoid Wilms tumors. 77/739 patients (10.4%) showed at least one Wilms tumor with a botryoid pattern, and they were sub-classified according to the SIOP criteria as follows: 28 stromal, 21 mixed, 7 regressive, 3 completely necrotic, 4 blastemal, 2 epithelial, 3 diffuse anaplasia, 1 focal anaplasia, and 10 non-anaplastic type (treated with primary surgery). Stage was as follows: 25 stage I, 21 stage II, 12 stage III, 11 stage IV, and 8 stage V. In six cases, local pathologists incorrectly upstaged the tumor from stage I to stage II based on botryoid growth. The event-free and overall survivals were 90 and 96%, respectively. We concluded that botryoid growth pattern is a common finding in Wilms tumor and that all histological types and stages can share this feature. The botryoid growth itself is not a criterion for stage II. Botryoid Wilms tumor is not an entity but merely represents a pattern of tumor growth; such tumors should be sub-classified according to their overall histological features, which will determine treatment and prognosis.

Aldrink JH, Cost NG, McLeod DJ, et al.
Technical Considerations for Nephron-Sparing Surgery in Children: What Is Needed to Preserve Renal Units?
J Surg Res. 2018; 232:614-620 [PubMed] Related Publications
BACKGROUND: Chemotherapy is used preoperatively for children with bilateral Wilms tumor (BWT) or unilateral high-risk Wilms tumor (UHRWT) to promote tumor regression to facilitate renal preservation with nephron-sparing surgery (NSS). In adults, various surgical techniques have been described to preserve renal tissue. Few studies have examined the use of surgical adjuncts in NSS in children with renal tumors.
METHODS: We performed a multi-institutional retrospective review of patients with BWT or UHRWT. Patient demographics, tumor size at diagnosis, following neoadjuvant chemotherapy, utilization of surgical adjuncts including intraoperative ultrasound (IOUS), margin status, complications, renal function, and follow-up were recorded.
RESULTS: The cohort comprised 23 patients: 18 BWT, 3 UHRWT, and 2 patients with solitary kidney. Twenty-two of the 23 patients had successful NSS. IOUS was used 19 times, and seven had positive margins after surgery. Cooling/vascular isolation was used six times. At a median follow-up of 18 mo, median estimated glomerular filtration rate Schwartz was 126 mL/min/1.73 m
CONCLUSIONS: In patients with BWT and UHRWT, surgical adjuncts such as cooling/vascular isolation are uncommonly performed. IOUS may be helpful but does not guarantee negative microscopic margins.
LEVEL OF EVIDENCE: Level 4, Case series with no comparison group.

Neal C, Rusangwa C, Borg R, et al.
Cost of Treating Pediatric Cancer at the Butaro Cancer Center of Excellence in Rwanda.
J Glob Oncol. 2018; 4:1-7 [PubMed] Related Publications
PURPOSE: Improvements in childhood survival rates have been achieved in low- and middle- income countries that have made a commitment to improve access to cancer care. Accurate data on the costs of delivering cancer treatment in these settings will allow ministries of health and donors to accurately assess and plan for expansions of access to care. This study assessed the financial cost of treating two common pediatric cancers, nephroblastoma and Hodgkin lymphoma, at the Butaro Cancer Center of Excellence in rural Rwanda.
METHODS: A microcosting approach was used to calculate the per-patient cost for Hodgkin lymphoma and nephroblastoma diagnosis and treatment. Costs were analyzed retrospectively from the provider perspective for the 2014 fiscal year. The cost per patient was determined using an idealized patient receiving a full course of treatment, follow-up, and recommended social support in accordance with the national treatment protocol for each cancer.
RESULTS: The cost for a full course of treatment, follow-up, and social support was determined to be between $1,490 and $2,093 for a patient with nephroblastoma and between $1,140 and $1,793 for a pediatric patient with Hodgkin lymphoma.
CONCLUSION: Task shifting, reduced labor costs, and locally adapted protocols contributed to significantly lower costs than those seen in middle- or high-income countries.

Kurose N, Takenaka M, Yamashita M, et al.
A case report of infantile cystic nephroblastoma.
Diagn Pathol. 2018; 13(1):84 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
BACKGROUND: Nephroblastoma (NB) is a malignant embryonal neoplasm derived from nephrogenic blastemal cells. NB usually forms a solid mass, but in extremely rare cases, it may show cystic changes.
CASE PRESENTATION: A six-month-old girl with persistent high fevers was found to have pyuria and bacteriuria. Ultrasonography revealed multilocular cysts in the right kidney. Right nephrectomy was performed with cyst wall rupture during surgery. An intraoperative rapid diagnosis, based on peritoneal fluid cytology, confirmed three components of blastemal, stromal, and epithelial cells. The blastemal cells were dyshesive, with scant to no cytoplasm and were the predominant cell type. The spindle-shaped stromal cells were arranged in fascicles. The epithelial cells demonstrated tubular structures. Macroscopically, the resected cystic tumor measured 80 mm in maximum diameter with a prominently thin cyst wall, but solid areas were also apparent. Histologically, the tumor was diagnosed as cystic NB (blastemal-predominant) displaying a triphasic pattern. Hyperchromatic nuclei and apoptotic bodies were found. The clinical stage classification of Japan Wilms Tumor Study group was 3. The patient was treated with chemotherapy and radiotherapy. Tumor recurrence and metastasis have not been observed in the 8 months since surgery.
CONCLUSION: This is an extremely rare case of infantile cystic NB. We diagnosed the NB cells that appeared in the peritoneal fluid by intraoperative rapid cytology. Cytological examination proved to be a very useful technique for determining the clinical stage of NB. Additionally, we propose that massive tumor degeneration and necrosis be considered as a pathogenic mechanism of cyst formation in NB.

Kruber P, Angay O, Winkler A, et al.
Loss or oncogenic mutation of DROSHA impairs kidney development and function, but is not sufficient for Wilms tumor formation.
Int J Cancer. 2019; 144(6):1391-1400 [PubMed] Related Publications
Wilms tumor (WT) is the most common kidney cancer in childhood. Mutations in the microprocessor genes DROSHA and DGCR8 have been identified as putative oncogenic drivers, indicating a critical role of aberrant miRNA processing in WT formation. To characterize the in vivo role of DROSHA mutations during kidney development and their oncogenic potential, we analyzed mouse lines with either a targeted deletion of Drosha or an inducible expression of human DROSHA carrying a tumor-specific E1147K mutation that acts in a dominant negative manner. Both types of mutation induce striking changes in miRNA patterns. Six2-cre mediated deletion of Drosha in nephron progenitors led to perinatal lethality with apoptotic loss of progenitor cells and early termination of nephrogenesis. Mosaic deletions via Wt1-cre

Loke BN, Wong MK, Tawng KD, et al.
Clinical, pathological and loss of heterozygosity differences in Wilms tumors between Asian and non-Asian children.
Int J Cancer. 2019; 144(6):1234-1242 [PubMed] Related Publications
Wilms tumor demonstrates significant interethnic epidemiological, histological and outcome differences, and is rare and poorly studied among Asians. We compared the clinicopathological, and loss of heterozygosity (LOH) profile and survival outcomes of Asian and non-Asian patients with Wilms tumor. Clinical charts and histological slides from patients with malignant renal tumors over a period of 20 years were retrospectively reviewed. We adapted a genotyping assay to determine 1p36 and 16q21-22 LOH in formalin-fixed paraffin-embedded (FFPE) specimens, and compared these characteristics between Asian and non-Asian patients. Fifty-three (79.1%) Asian and 14 (20.9%) non-Asian patients had Wilms tumors. Compared to non-Asians, Asians were younger (mean 4.6 and 4.0 years, respectively), had more equal gender distribution (female: male = 1.8 and 1.0, respectively), fewer tumors with unfavorable histology (25.0% and 4.1%, respectively, p = 0.05), and less advanced disease at presentation, yet similar nodal metastases rates (16.7% and 18.4%, respectively). No Asian patients had bilateral tumors. Our adapted genotyping assay accurately determined LOH in FFPE specimens <10 years post-fixation. Among 30 Asian patients, 1p and 16q LOH were each detected in 5 (16.7%) patients, respectively-similar to rates reported in other ethnicities. Yet after similar treatment with National Wilms Tumor Study regimens, 15-year event-free and overall survival for Asian patients was 95.7% and 96.3% respectively. In summary, despite similar nodal metastasis and LOH rates, Asian patients had fewer unfavorable histology tumors, lower-stage disease, and better survival outcomes. The bases for these differences and implications on treatment strategy for these patients warrant further study.

Guo F, Li T, Liu W, et al.
Wilms tumor with inferior vena cava duplication: a rare case report.
BMC Urol. 2018; 18(1):88 [PubMed] Article available free on PMC after 01/06/2020 Related Publications
BACKGROUND: Wilms tumor is the most common renal tumor of childhood. Duplication of the inferior vena cava is an uncommon anomaly. In the present study, we present a case of Wilms tumor with the inferior vena cava duplication, which has not been reported previously.
CASE PRESENTATION: A 14-month-old female presented with an enlarging abdominal mass. Computed tomography imaging demonstrated a large mass in the right kidney, duplication of the inferior vena cava below the renal veins and compression of the right inferior vena cava caused by the enormous mass. A right radical nephrectomy was performed. Final pathology was consistent with Wilms tumor. Postoperative adjuvant chemotherapy was executed. Computed tomography imaging at 3 months postoperatively showed the right inferior vena cava played a dominant role and the left inferior vena cava was not detected clearly. During the follow-up of 18 months, no local recurrence or metastasis has been observed.
CONCLUSION: It is important to recognize the case of Wilms tumor with the inferior vena cava duplication to avoid injury of retroperitoneal venous anomalies and life-threatening hemorrhage during surgery through preoperative computed tomography.

Han Q, Li K, Dong K, et al.
Clinical features, treatment, and outcomes of bilateral Wilms' tumor: A systematic review and meta-analysis.
J Pediatr Surg. 2018; 53(12):2465-2469 [PubMed] Related Publications
BACKGROUND: Wilms' tumor(WT) is the most common malignant renal tumor of childhood. Despite the good prognosis of WT, bilateral Wilms' tumor (BWT) still has a poor outcome. We systematically reviewed the literature on BWT, aiming to define its clinical features, treatment, and outcomes.
METHODS: PubMed, OVID EMbase, Web of Science, and Cochrane Library were systematically searched for studies published from 1980 to 2017. Case series and comparative studies reported clinical data of BWT patients were included.
RESULTS: A total of 32 studies comprising 1457 patients were retained for primary outcome. Hemihypertrophy, cryptorchidism, and Beckwith-Wiedemann syndrome(BWS) are the most common congenital anomalies and syndrome. 86% of patients had favorable histology (FH). Patients with local stage I or II accounted for 64%, and 12.6% had metastasis at diagnosis. Bilateral nephron-sparing surgery (NSS) was achieved in 33.8%. Recurrence and renal failure occurred in 20% and 8%. The overall survival (OS) was 73%. In comparative studies, OS of patients undergoing bilateral NSS was similar to that of other operation types.
CONCLUSION: Prognosis of BWT has been improved but is significantly poorer than WT. Bilateral NSS was recommended by most centers to preserve more renal volume. However, finding a balance between retaining renal function and avoiding recurrence remains a question.
TYPE OF STUDY: Systematic review.

Aldrink JH, Heaton TE, Dasgupta R, et al.
Update on Wilms tumor.
J Pediatr Surg. 2019; 54(3):390-397 [PubMed] Related Publications
This article reviews of the current evidence-based treatment standards for children with Wilms tumor. In this article, a summary of recently completed clinical trials by the Children's Oncology Group is provided, the current diagnostic evaluation and surgical standards are discussed, and the surgical impact on current risk stratification for patients with Wilms tumor is highlighted. LEVEL OF EVIDENCE: This is a review article of previously published and referenced LEVEL 1 studies, but also includes expert opinion LEVEL V, represented by the American Pediatric Surgical Association Cancer Committee.

Friesenbichler W, Krizmanich W, Lakatos K, et al.
Outcome of two patients with bilateral nephroblastomatosis/Wilms tumour treated with an add-on 13-cis retinoic acid therapy - Case report.
Pediatr Hematol Oncol. 2018; 35(3):218-224 [PubMed] Related Publications
Although the fate of nephrogenic rests varies, they are known to be precursors of Wilms tumour. Thus, nephrogenic rests require adequate treatment to prevent malignant transformation. We added 13-cis retinoic acid to the standard chemotherapy with vincristine and actinomycin-D in two patients with bilateral nephrogenic rests/nephroblastomatosis. Patient 1 also had a history of Wilms tumour. 46 (patient 1) and 81 (patient 2) months after end of treatment, both patients show stable conditions with no signs of relapse or progressive disease. Our observation supports further investigation of retinoic acid in patients with nephrogenic rests and nephroblastomatosis.

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