title: p53 expression predicts dismal outcome for medulloblastoma patients with metastatic disease.
abstract: Medulloblastoma (MB) is the most common malignant primary brain tumour in childhood. Metastatic disease (M+) at diagnosis is the most important negative prognostic clinical marker and, despite craniospinal irradiation and intensive chemotherapy, it remains one of the leading causes of treatment failure. To date, few clinical and biological data have been evaluated to obtain an additional prognostic profile for these high-risk patients. In this study, 169 patients with metastatic MB registered in the multicentre HIT2000 trial of the German Society of Pediatric Oncology and Haematology (GPOH) have been investigated to determine the importance of p53 protein expression in predicting survival. At a median follow-up of 4.1 years, 159 patients with p53-negative tumours had significantly better four-year event-free survival (EFS) and progression-free survival (PFS) (56 ± 11, 59 ± 4%) than 10 patients with p53-positive tumours (40 ± 16, 40 ± 16%; P = 0.018 for EFS, P = 0.007 for PFS, respectively). Furthermore, four-year overall survival (OS) of children with p53-negative tumours was higher than for children with p53-positive tumours (72 ± 4 vs. 35 ± 18%, P = 0.05). Three of the p53-positive MBs harbored a point mutation in the TP53 gene. p53 protein assessment by immunohistochemistry may be a useful tool for sub-stratification of metastatic high-risk MB patients.
authors.affiliation: Institute of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. mgessimd@yahoo.com
authors.forename: Marco
authors.initials: M
authors.lastname: Gessi
authors.forename: André O
authors.initials: AO
authors.lastname: von Bueren
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor; D002528:Cerebellar Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011237:Predictive Value of Tests; D016019:Survival Analysis; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D051176:beta Catenin