Aberrant p53, mdm2, and proliferation differ in glioblastomas from long-term compared with typical survivors.
OBJECTIVE
Glioblastoma multiforme (GBM) is a highly lethal neoplasm with a median survival of approximately 1 year. Only 2-5% of patients originally diagnosed with GBM will survive > or = 3 years. Whether tumors from these long-term survivors (LTSs) exhibit molecular genetic differences compared with typical GBM survivors is not known.


METHODS
Tumors from 41 patients initially diagnosed with GBM and having survival > or = 3 years (LTS) was compared with 48 GBMs from short-term survivors (STSs, survival < or = 1.5 years) for p53 aberrations (expression/mutation), epidermal growth factor receptor overexpression, mdm2 overexpression, and proliferation index.


RESULTS
Nuclear p53 expression was significantly more frequent in the LTS group. However, no difference in the rate of p53 mutation was evident. Overexpression of epidermal growth factor receptor was slightly more frequent in the STS patients, but this is not statistically different. mdm2 overexpression was significantly more frequent in the STSs, and this group had a significantly higher median proliferation index.


CONCLUSIONS
Long-term GBM survivors were more likely to have p53-overexpressing tumors, although a difference in p53 mutation rate could not be detected. They were less likely to exhibit mdm2 overexpression and had a lower proliferation rate compared with typical GBM survivors.
Burton
Eric C
EC
Department of Pathology, University of California, San Francisco, San Francisco, California 94143, USA.
Lamborn
Kathleen R
KR
Forsyth
Peter
P
Scott
James
J
O'Campo
Jason
J
Uyehara-Lock
Jane
J
Prados
Michael
M
Berger
Mitchel
M
Passe
Sandra
S
Uhm
Joon
J
O'Neill
Brian P
BP
Jenkins
Robert B
RB
Aldape
Ken D
KD
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D017741:Survivors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D066246:ErbB Receptors