title: Worse outcome in primary glioblastoma multiforme with concurrent epidermal growth factor receptor and p53 alteration.
abstract: Primary glioblastoma multiforme (GBM), in contrast with secondary GBM, has been associated with the presence of EGFR amplification and absence of p53 mutation. In this study, we analyzed relevant molecular and clinical variables in 194 primary GBMs and tested them for survival analysis. Although most of the tumors showed a mutually exclusive pattern, concurrent alterations of EGFR and p53 were detected. Survival analysis of CDK4 amplification revealed a highly significant association with a worse clinical outcome (P = .01), whereas MDM2, CDK6, PTEN, and p21 were not associated with patient survival. Multivariate analysis including the significant clinical and molecular variables revealed CDK4 amplification, age, and radiotherapy to be markers with independent prognostic value. In addition, the primary GBM tumors showing simultaneous EGFR and p53 alterations were significantly associated with worse survival (P < .01). These results highlight the prognostic value of CDK4 amplification and of simultaneous EGFR-p53 alterations in the clinical outcome of patients with primary GBM.
authors.affiliation: Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Ruano
authors.forename: Teresa
authors.initials: T
authors.lastname: Ribalta
authors.forename: Angel Rodríguez
authors.initials: AR
authors.lastname: de Lope
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos-Martín
authors.forename: Concepción
authors.initials: C
authors.lastname: Fiaño
authors.forename: Elisa
authors.initials: E
authors.lastname: Pérez-Magán
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Hernández-Moneo
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.forename: Bárbara
authors.initials: B
authors.lastname: Meléndez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4