[Clinical and pathological significance of p53 gene mutation in human cerebral glioblastoma multiforme].
Cerebral glioblastomas multiforme (GMs), the most malignant human primary brain tumor, molecular genetically comprise two subsets characterized by p53 tumor suppressor gene status. One is characterized by p53 mutation and another is with wild-type p53 and overexpression of epidermal growth factor receptor (EGFR). We analyzed the p53 status by a highly reliable yeast-based assay, overexpression of EGFR by immunohistochemistry, and their relations to clinical outcome along with other several clinical parameters, in a total of 42 patients with GMs. We found p53 mutations in 18 cases (43%) of 42 GMs and overexpression of EGFR in 16 cases (43%) of 37 GMs. The tumors with p53 mutation were associated with younger onset ages and longer survival. We also analyzed their survival and radiation sensitivity relative to p53 status, EGFR and other prognostic factors, including onset age, extent of surgery, post-operative Karnofsky performance score (KPS), and location of tumor. Log-rank tests showed that younger onset ages (below 50 years; p < 0.0111), p53 mutation (p < 0.0005), superficial tumor location (p < 0.0026) and post operatives KPS (over 80%; p < 0.0147) correlated with longer survival. Multivariate Cox regression analysis identified the absence of p53 mutation (p < 0.0335) and the deep tumor location (p < 0.0297) as the independent, adverse prognostic factors. Tumor response to radiation was assessed by progression-free period (time to progression; TTP). A significant correlation was found between TTP and survival (p < 0.0001). Log-rank tests and multivariate Cox regression analysis showed that younger onset ages (below 50 years; p < 0.0145), p53 mutation (p < 0.0001), radical resection (p < 0.0198) and post operative KPS (over 80%; p < 0.0001) correlated with radiation sensitivity, and identified the absence of p53 mutation (p < 0.0146) as the sole independent hazard for radiation response. In conclusion, p53 mutation confers radiation sensitivity in GMs, which results in patients' longer survival.
Matsumoto
R
R
Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan.
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D016158:Genes, p53; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012044:Regression Analysis
D066246:ErbB Receptors