Worse outcome in primary glioblastoma multiforme with concurrent epidermal growth factor receptor and p53 alteration.
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.
Ruano
Yolanda
Y
Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo, Spain.
Ribalta
Teresa
T
de Lope
Angel Rodríguez
AR
Campos-Martín
Yolanda
Y
Fiaño
Concepción
C
Pérez-Magán
Elisa
E
Hernández-Moneo
José-Luis
JL
Mollejo
Manuela
M
Meléndez
Bárbara
B
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
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4