title: Molecular risk stratification of medulloblastoma patients based on immunohistochemical analysis of MYC, LDHB, and CCNB1 expression.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Human Genetics, Neuropathology, and Neurogenetics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Talitha
authors.initials: T
authors.lastname: de Haas
authors.forename: Nancy
authors.initials: N
authors.lastname: Hasselt
authors.forename: Dirk
authors.initials: D
authors.lastname: Troost
authors.forename: Huib
authors.initials: H
authors.lastname: Caron
authors.forename: Mara
authors.initials: M
authors.lastname: Popovic
authors.forename: Lorna
authors.initials: L
authors.lastname: Zadravec-Zaletel
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Grajkowska
authors.forename: Marta
authors.initials: M
authors.lastname: Perek
authors.forename: Maria-Chiara
authors.initials: MC
authors.lastname: Osterheld
authors.forename: David
authors.initials: D
authors.lastname: Ellison
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D019926:Cyclin B / Q000096:biosynthesis*; D056744:Cyclin B1; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007223:Infant; D007527:Isoenzymes / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis*; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis* / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D012306:Risk
chemical_list: C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D007527:Isoenzymes; D016271:Proto-Oncogene Proteins c-myc; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1