The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
β-Catenin Status Predicts a Favorable Outcome in Childhood Medulloblastoma: The United Kingdom Children's Cancer Study Group Brain Tumour Committee
Abstract
Purpose: Identifying pathobiological correlates of clinical behavior or therapeutic response currently represents a key challenge for medulloblastoma research. Nuclear accumulation of the β-catenin protein is associated with activation of the Wnt/Wg signaling pathway, and mutations affecting components of this pathway have been reported in approximately 15% of sporadic medulloblastomas. We tested the hypothesis that nuclear immunoreactivity for β-catenin is a prognostic marker in medulloblastoma, and assessed the relationship between nuclear β-catenin immunoreactivity and mutations of CTNNB1 and APC. Patients and Methods: Medulloblastomas from children entered onto the International Society for Pediatric Oncology (SIOP)/United Kingdom Children's Cancer Study Group (UKCCSG) PNET3 trial (n = 109) were examined for β-catenin immunoreactivity, and where tissue was available, evidence of CTNNB1 and APC mutations. The results were correlated with clinicopathologic variables, principally outcome. Results: Children with medulloblastomas that showed a nucleopositive β-catenin immunophenotype (27 of 109; 25%) had significantly better overall (OS) and event-free (EFS) survivals than children with tumors that showed either membranous/cytoplasmic β-catenin immunoreactivity or no immunoreactivity (P = .0015 and P = .0026, respectively). For β-catenin nucleopositive and nucleonegative medulloblastomas, 5-year OS was 92.3% (95% CI, 82% to 100%) versus 65.3% (95% CI, 54.8 to 75.7%), and 5-year EFS was 88.9% (95% CI, 77% to 100%) versus 59.5% (95% CI, 48.8 to 70.2%), respectively. Mutations in CTNNB1 were found exclusively among medulloblastomas that demonstrated nuclear β-catenin immunoreactivity, but no evidence of APC mutation was found in these cases. All children with β-catenin nucleopositive large cell/anaplastic medulloblastomas and β-catenin nucleopositive medulloblastomas presenting with metastatic disease are alive at least 5 years postdiagnosis. Conclusion: Nuclear accumulation of β-catenin appears to be a marker of favorable outcome in medulloblastoma, and should be investigated further in large group-wide trials.
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Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities
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Self-citationRisk stratification of childhood medulloblastoma in the molecular era: the current consensus
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Metadata
- Authors
- Ellison, D. W., Onilude, O. E., Lindsey, J. C., Lusher, M. E., Weston, C. L., Taylor, R. E., Pearson, A. D., & Clifford, S. C.
- Venue
- Journal of Clinical Oncology
- Published
- 2005-11-01
- Volume
- 23
- Issue
- 31
- Pages
- 7951-7957
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2139787372
- Cited by
- 435
- References
- 35
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- closed
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- Ellison, D. W., Onilude, O. E., Lindsey, J. C., Lusher, M. E., Weston, C. L., Taylor, R. E., Pearson, A. D., & Clifford, S. C. (2005). β-Catenin Status Predicts a Favorable Outcome in Childhood Medulloblastoma: The United Kingdom Children's Cancer Study Group Brain Tumour Committee. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2005.01.5479
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