title: Age-dependent prognostic effects of EGFR/p53 alterations in glioblastoma: study on a prospective cohort of 140 uniformly treated adult patients.
abstract: OBJECTIVE
  To assess the prognostic influence of EGFR amplification/overexpression, p53 immunoreactivity and their age-dependent prognostic effects in a large prospective cohort of uniformly treated adult patients with newly diagnosed glioblastoma.
  
  
  METHODS
  Tumours from a uniformly treated prospective cohort of adult patients with newly diagnosed glioblastoma (n=140) were examined for EGFR amplification by fluorescence in situ hybridisation and EGFR/p53 expression by immunohistochemistry. Statistical methods were employed to assess the degree of association between EGFR amplification/overexpression and p53 immunopositivity. Survival analyses were performed by employing Cox proportional hazard models to assess the independent prognostic value of EGFR/p53 alterations and test the propensity for risk with age by assessing their interaction with patient age.
  
  
  RESULTS
  A strong positive correlation between EGFR amplification and EGFR overexpression (rho=0.5157; p<0.0001; CI 0.3783 to 0.6309) and a negative association of EGFR amplification (rho=-0.3417; p<0.0001; CI -0.4842 to -0.1816) and EGFR overexpression (rho=-0.3095; p<0.001; CI -0.4561 to -0.1465) with p53 immunopositivity was observed. Only patient age (HR: 1.029; p=0.004; CI 1.009 to 1.049) was associated with shorter survival by univariate Cox regression analysis. Multivariable Cox proportional hazards models revealed a statistically significant interaction between EGFR overexpression and age to be associated with shorter survival (HR: 1.001; p<0.0001; CI 1.000 to 1.002), thus predicting a higher hazard with increasing age. No age interaction of EGFR amplification status (HR: 1.001; p=0.642; CI 0.995 to 1.008) and p53 immunopositivity (HR: 1.000; p=0.841; CI 0.999 to 1.001) was noted in this cohort.
  
  
  CONCLUSIONS
  The prognostic value of EGFR overexpression is age-dependent, and there is a propensity for a higher hazard with increasing patient age. Identifying such groups of patients with more aggressive disease becomes mandatory, since they would benefit from intense therapeutic protocols targeting EGFR.
authors: Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India.
authors: M R
authors: MR
authors: Srividya
authors: Balaram
authors: B
authors: Thota
authors: A
authors: A
authors: Arivazhagan
authors: K
authors: K
authors: Thennarasu
authors: A
authors: A
authors: Balasubramaniam
authors: B A
authors: BA
authors: Chandramouli
authors: A S
authors: AS
authors: Hegde
authors: V
authors: V
authors: Santosh
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D004812:Epidemiologic Methods; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D016158:Genes, p53; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors