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Age-dependent prognostic effects of EGFR/p53 alterations in glioblastoma: study on a prospective cohort of 140 uniformly treated adult patients
  1. M R Srividya1,
  2. Balaram Thota1,
  3. A Arivazhagan2,
  4. K Thennarasu3,
  5. A Balasubramaniam2,
  6. B A Chandramouli2,
  7. A S Hegde4,
  8. V Santosh1
  1. 1Departments of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India
  2. 2Departments of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India
  3. 3Departments of Biostatistics, National Institute of Mental Health and Neurosciences, Bangalore, India
  4. 4Department of Neurosurgery, Sri Satya Sai Institute of Higher Medical Sciences, Bangalore, India
  1. Correspondence to Dr Vani Santosh, Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India; vani.santosh{at}gmail.com

Abstract

Aims 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 (ρ=0.5157; p<0.0001; CI 0.3783 to 0.6309) and a negative association of EGFR amplification (ρ=−0.3417; p<0.0001; CI −0.4842 to −0.1816) and EGFR overexpression (ρ=−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.

  • Fluorescence in situ hybridisation
  • glioblastoma
  • survival
  • age dependency
  • genetic alteration
  • immunohistochemistry
  • prognosis
  • EGFR
  • fish
  • neuro-oncology
  • P53

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Footnotes

  • Funding This study was partially funded by the NMITLI programme of the Council of Scientific and Industrial Research, India.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by NIMHANS and SSIHMS, Bangalore, India.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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