Abstract 2649: Expression and prognostic value of EGR1 and EGR3 in gliomas
Authors: Knudsen Arnon M. , Eilertsen Ida , Kielland Susanne , Boldt Henning B. , Mellegaard Caspar S. , Munthe Sune , Kristensen Bjarne W. 
Published: August 2018

Introduction

Gliomas are the most frequent primary brain tumors. For the most malignant glioma - the glioblastoma - the median survival is below 15 months. Since only few prognostic biomarkers are of benefit in daily practice, new markers are urgently needed. EGR1 and EGR3 are transcription factors involved in the regulation of cell-cycle and cell differentiation, but they have also been associated with migration of cancer cells. Studies have shown prognostic potential of EGR1 and EGR3 in breast-, gastric-, colorectal-, and prostate cancer. The purpose of this study was to investigate the expression and potential prognostic value of EGR1 and EGR3 in gliomas.

Methods

Samples of 214 gliomas were stained with anti-EGR1 and -EGR3 antibodies respectively. The stainings were assessed with a software-based digital classifier and a semi-quantitative scoring system. Kaplan-Meier estimates and Log-rank tests were used to compare survival distributions, and ROC-curve analysis with dichotomizing was applied to identify optimal cut-off values. Cox proportional hazards regression was performed to further investigate and identify independent prognostic variables.

Results

Both EGR1 and EGR3 were expressed in all glioma samples, but with considerable variation between tumors. EGR1 expression ranged from 1-83% positive cells and increased with WHO grade, while EGR3 expression ranged from 5-95% positive cells independent of WHO grade. High EGR1 levels were associated with improved survival in glioblastomas, while low EGR3 levels were associated with improved survival in WHO grade II and III gliomas. In glioblastomas, the EGR1 high/EGR3 low group was associated with improved patient survival when compared to the EGR1 low/EGR3 high group. Similar results were found in MGMT-promoter methylated glioblastomas, but not in MGMT-unmethylated glioblastomas. Cox proportional hazards regression showed that a high EGR1 fraction remained a significant prognostic variable when adjusted for confounders, both in all gliomas as one group (P=0.048) and glioblastomas exclusively (P=0.011). The combination of EGR1 high/EGR3 low in glioblastomas also remained significant after adjustment for confounders (P=0.030).

Conclusion

Both EGR1 and EGR3 proteins were expressed in all investigated gliomas. High levels of EGR1 seemed to be associated with improved patient survival in glioblastomas. In MGMT-promoter methylated glioblastomas, the EGR1 high/EGR3 low group was associated with improved patient survival when compared to the EGR1 low/EGR3 high group. Validation of the results in an additional patient cohort is needed, including analysis of prognostic value in different types of grade II and III gliomas.

Citation Format: Arnon M. Knudsen, Ida Eilertsen, Susanne Kielland, Henning B. Boldt, Caspar S. Mellegaard, Sune Munthe, Bjarne W. Kristensen. Expression and prognostic value of EGR1 and EGR3 in gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2649.