Molecular risk stratification of medulloblastoma patients based on immunohistochemical analysis of MYC, LDHB, and CCNB1 expression.

Détails

ID Serval
serval:BIB_947ACA0E049A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Molecular risk stratification of medulloblastoma patients based on immunohistochemical analysis of MYC, LDHB, and CCNB1 expression.
Périodique
Clinical Cancer Research
Auteur⸱e⸱s
de Haas T., Hasselt N., Troost D., Caron H., Popovic M., Zadravec-Zaletel L., Grajkowska W., Perek M., Osterheld M.C., Ellison D., Baas F., Versteeg R., Kool M.
ISSN
1078-0432
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
14
Numéro
13
Pages
4154-4160
Langue
anglais
Résumé
PURPOSE: Medulloblastoma is the most common malignant embryonal brain tumor in children. The current clinical risk stratification to select treatment modalities is not optimal because it does not identify the standard-risk patients with resistant disease or the unknown number of high-risk patients who might be overtreated with current protocols. The aim of this study is to improve the risk stratification of medulloblastoma patients by using the expression of multiple prognostic markers in combination with current clinical parameters. EXPERIMENTAL DESIGN: Candidate prognostic markers were selected from literature or from medulloblastoma expression data. Selected genes were immunohistochemically analyzed for their prognostic value using medulloblastoma tissue arrays containing 124 well-characterized patient samples. RESULTS: Protein expression analyses showed that the combined expression of three genes was able to predict survival in medulloblastoma patients. Low MYC expression identified medulloblastoma patients with a very good outcome. In contrast, concomitant expression of LDHB and CCNB1 characterized patients with a very poor outcome. Multivariate analyses showed that both expression of MYC and the LDHB/CCNB1 gene signature were strong prognostic markers independent of the clinical parameters metastasis and residual disease. Combined analysis of clinical and molecular markers enabled greater resolution of disease risk than clinical factors alone. CONCLUSIONS: A molecular risk stratification model for medulloblastoma patients is proposed based on the signature of MYC, LDHB, and CCNB1 expression. Combined with clinical variables, the model may provide a more accurate basis for targeting therapy in children with this disease.
Mots-clé
Adolescent, Brain Neoplasms/metabolism, Child, Child, Preschool, Cyclin B/biosynthesis, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry/methods, Infant, Isoenzymes/biosynthesis, L-Lactate Dehydrogenase/biosynthesis, Male, Medulloblastoma/diagnosis, Medulloblastoma/metabolism, Proto-Oncogene Proteins c-myc/biosynthesis, Risk
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/07/2008 10:50
Dernière modification de la notice
20/08/2019 14:57
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