Faculty Opinions recommendation of beta-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee.

Author(s):  
Eric Bouffet ◽  
Jennifer Adamski
2005 ◽  
Vol 23 (31) ◽  
pp. 7951-7957 ◽  
Author(s):  
David W. Ellison ◽  
Olabisi E. Onilude ◽  
Janet C. Lindsey ◽  
Meryl E. Lusher ◽  
Claire L. Weston ◽  
...  

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.


1997 ◽  
Vol 15 (7) ◽  
pp. 2622-2630 ◽  
Author(s):  
A G Shankar ◽  
S Ashley ◽  
M Radford ◽  
A Barrett ◽  
D Wright ◽  
...  

PURPOSE Histology has been identified as an important prognostic factor in Hodgkin's disease (HD) in adults. Information regarding the impact of histology on outcome in childhood HD is scarce. This study determines the effect of histology on the overall survival (OS) or progression-free survival (PFS) in a national series of children treated in a standardized manner. PATIENTS AND METHODS The results of treatment of 331 assessable patients, treated between January 1, 1982 and June 30, 1992, in the United Kingdom Children's Cancer Study Group (UKCCSG) Hodgkin's study I were reviewed to evaluate OS, PFS, and deaths according to stage and histology. Treatment was either involved-field radiation alone (stage IA) or chlorambucil, vinblastine, procarbazine, and prednisolone (ChlVPP) chemotherapy with or without mediastinal radiation. All were clinically staged at diagnosis. RESULTS Nodular sclerosing (NS) HD was the most common histologic subtype (155 of 331 patients [47%]) and was uniformly distributed through all stages. Lymphocyte-depletion (LD) HD was extremely uncommon (< 1%). Mixed-cellularity (MC) HD had the highest relapse rate, but this was only significant (P < .05) in stage I patients who received local irradiation alone. There was no other statistically significant difference in OS and PFS between the various histologic subtypes. Multivariate analysis for PFS and OS confirmed that stage was the most important prognostic factor and that histology did not have an effect after stratification by stage. CONCLUSION This study demonstrates that with effective multiagent chemotherapy, histologic subtype does not influence outcome. The high relapse rates in stage I MC subtype indicates that MC HD is biologically aggressive and systemic treatment with or without local irradiation may be indicated. The high relapse rate in stage IV patients appeared to be independent of histology.


1990 ◽  
Vol 65 (9) ◽  
pp. 968-970 ◽  
Author(s):  
J J Groot-Loonen ◽  
C R Pinkerton ◽  
P H Morris-Jones ◽  
J Pritchard

2003 ◽  
Vol 21 (17) ◽  
pp. 3269-3275 ◽  
Author(s):  
K. Pritchard-Jones ◽  
A. Kelsey ◽  
G. Vujanic ◽  
J. Imeson ◽  
C. Hutton ◽  
...  

Purpose: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms’ tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. Patients and Methods: During two consecutive trials of the United Kingdom Children’s Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms’ tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. Results: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P = .001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P = .01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P = .66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). Conclusion: Treatment for stage I FH Wilms’ tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms’ tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.


1984 ◽  
Vol 50 (4) ◽  
pp. 457-462 ◽  
Author(s):  
M G Mott ◽  
J M Chessells ◽  
M L Willoughby ◽  
J R Mann ◽  
P H Morris-Jones ◽  
...  

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