Age-dependent Prognostic Effects of EGFR/p53 Alterations in Glioblastoma: Study on a Prospective Cohort of 140 Uniformly Treated Adult Patients

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 (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.