| Molecular characterization of Wilms' tumor from a resource-constrained region of sub-Saharan Africa. | |
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MedLine Citation:
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PMID: 22437966 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sub-Saharan African children have an increased incidence of Wilms' tumor (WT) and experience alarmingly poor outcomes. Although these outcomes are largely due to inadequate therapy, we hypothesized that WT from this region exhibits features of biological aggressiveness that may warrant broader implementation of high-risk therapeutic protocols. We evaluated 15 Kenyan WT (KWT) for features of aggressive disease (blastemal predominance and Ki67/cellular proliferation) and treatment resistance (anaplasia and p53 immunopositivity). To explore the additional biological features of KWT, we determined the mutational status of the CTNNB1/β-catenin and WT1 genes and performed immunostaining for markers of Wnt pathway activation (β-catenin) and nephronic progenitor cell self-renewal (WT1, CITED1 and SIX2). We characterized the proteome of KWT using imaging mass spectrometry (IMS). The results were compared to histology- and age-matched North American WT (NAWT) controls. For patients with KWT, blastemal predominance was noted in 53.3% and anaplasia in 13%. We detected increased loss to follow-up (p = 0.028), disease relapse (p = 0.044), mortality (p = 0.001) and nuclear unrest (p = 0.001) in patients with KWT compared to controls. KWT and NAWT showed similar Ki67/cellular proliferation. We detected an increased proportion of epithelial nuclear β-catenin in KWT (p = 0.013). All 15 KWT specimens were found to harbor wild-type CTNNB1/β-catenin, and one contained a WT1 nonsense mutation. WT1 was detected by immunostaining in 100% of KWT, CITED1 in 80% and SIX2 in 80%. IMS revealed a molecular signature unique to KWT that was distinct from NAWT. The African WT specimens appear to express markers of adverse clinical behavior and treatment resistance and may require alternative therapies or implementation of high-risk treatment protocols. |
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Authors:
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Andrew J Murphy; Jason R Axt; Christian de Caestecker; Janene Pierce; Hernan Correa; Erin H Seeley; Richard M Caprioli; Mark W Newton; Mark P de Caestecker; Harold N Lovvorn |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-04-04 |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 131 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-07-23 Completed Date: 2013-03-11 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: E983-94 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 UICC. |
Affiliation:
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Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. andrew.j.murphy@vanderbilt.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Africa South of the Sahara Child, Preschool Female Genes, Wilms Tumor Humans Infant Kidney Neoplasms / genetics*, mortality, pathology Male Mass Spectrometry Mutation Nuclear Proteins / analysis Prognosis Transcription Factors / analysis Tumor Suppressor Protein p53 / analysis Wilms Tumor / genetics*, mortality, pathology beta Catenin / analysis, genetics |
| Grant Support | |
ID/Acronym/Agency:
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4R00CA135695-03/CA/NCI NIH HHS; 5T32CA106183-06A1/CA/NCI NIH HHS; KL2 RR024977/RR/NCRR NIH HHS; KL2 TR000446/TR/NCATS NIH HHS; P30-CA68485/CA/NCI NIH HHS; T32 CA106183-06A1/CA/NCI NIH HHS; TL1 RR024978/RR/NCRR NIH HHS; TL1 TR000447/TR/NCATS NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 TR000445/TR/NCATS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CITED1 protein, human; 0/CTNNB1 protein, human; 0/Nuclear Proteins; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/beta Catenin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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