The Role of EGFR Amplification in Deep Venous Thrombosis Occurrence in IDH Wild-Type Glioblastoma

Abstract

Introduction: Glioblastoma (GBM) patients have a 20–30 incidence of venous thromboembolic events. EGFR is a widely used prognostic marker for many cancers. Recent lung cancer studies have described relationships between EGFR amplification and an increased incidence of thromboembolic complications. We aim to explore this relationship in glioblastoma patients. Methods: Two hundred ninety-three consecutive patients with IDH wild-type GBM were included in the analysis. The amplification status of EGFR was measured using fluorescence in situ hybridization (FISH). Centromere 7 (CEP7) expression was recorded to calculate the EGFR-to-CEP7 ratio. All data were collected retrospectively through chart review. Molecular data were obtained through the surgical pathology report at the time of biopsy. Results: There were 112 subjects who were EGFR-amplified (38.2%) and 181 who were non-amplified (61.8%). EGFR amplification status was not significantly correlated with VTE risk overall (p = 0.2001). There was no statistically significant association between VTE and EGFR status after controlling for Bevacizumab therapy (p = 0.1626). EGFR non-amplified status was associated with an increased VTE risk in subjects greater than 60 years of age (p = 0.048). Conclusions: There was no significant difference in occurrence of VTE in patients with glioblastoma, regardless of EGFR amplification status. Patients older than 60 years of age with EGFR amplification experienced a lower rate of VTE, contrary to some reports on non-small-cell lung cancer linking EGFR amplification to VTE risk.

Incidence of venous thromboembolism and bleeding in patients with malignant central nervous system neoplasm: Systematic review and meta-analysis

“…In studies that provided incidence values by sex (n = 9), 62.7% of participants were men (n = 1,779). Only three studies presented data on patients aged 60 years or older (28,(31)(32), totaling 163 patients with VTE out of 446 patients with CNS (36.5%).…”

An MRI Radiomics Approach to Predict the Hypercoagulable Status of Gliomas

“…Activation of the Epidermal Growth Factor Receptor (EGFR), through genomic amplifications or mutations, was reported to be positively correlated with F3 expression in GBM [13]. A significant positive association between the amplification status of the EGFR locus in GBM and the presence of histologically detectable intra-tumoral thrombosis was suggested by Furuta et al [14]; however, the link between VTE and the presence of EGFR amplifications in GBM nevertheless remains uncertain [15,16]. In addition to specific genomic alterations, chromosomal instability also activates innate immune pathways, potentially leading to F3 expression in human tumors [17].…”

Untitled

“…In studies that provided incidence values by sex (n = 9), 62.7% of participants were men (n = 1,779). Only three studies presented data on patients aged 60 years or older (28,(31)(32), totaling 163 patients with VTE out of 446 patients with CNS (36.5%).…”