Prognostic and predictive value of p53 in low MGMT expressing glioblastoma treated with surgery, radiation and adjuvant temozolomide chemotherapy.
OBJECTIVE
To assess the prognostic and predictive significance of p53 protein expression in low O6-methylguanine-DNA methyltransferase (MGMT) expressing glioblastoma multiform (GBM) treated with combined therapy.


METHODS
The authors reviewed the clinical outcomes of 46 low MGMT expressing GBM patients who had undergone surgery, conventional local radiotherapy and temozolomide chemotherapy. Correlation between p53 expression level and clinical outcomes were analysed with univariate and multivariate Cox model.


RESULTS
Patients with low p53 expression had a significantly improved progression free survival (PFS) (p=0.015) and overall survival (OS) (p=0.047) compared to those with high expression. On both univariate and multivariate analyses, low p53 expression persisted as a significant independent favorable prognostic factor for PFS (p=0.017). Pre-operative Karnofsky performance status score (p=0.029), tumor resection extent (p=0.045) and p53 expression level (p=0.038) were significant independent prognostic factors for OS.


CONCLUSIONS
In these low MGMT expressing GBM patients with combined treatment, low p53 expression was a significant independent favorable prognostic factor for both PFS and OS. In addition to MGMT, p53 may be another stratification variable in the future therapeutic trials.
Li
Shouwei
S
Glioma Treatment Center, Beijing Tiantan Hospital, Capital University of Medical Sciences, Beijing, China.
Zhang
Wei
W
Chen
Baoshi
B
Jiang
Tao
T
Wang
Zhongcheng
Z
D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D000077204:Temozolomide; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide