Prognostic implications of epidermal growth factor receptor variant Ⅲ expression and nuclear translocation in Chinese human gliomas

作者：Kaiyuan Yang; Xiaohui Ren; Liyuan Tao; Peipei Wang; Haihui Jiang; Li Shen; Yiming Zhao; Yong Cui; Mingxiao Li; Song Lin^*

来源：Chinese Journal of Cancer Research, 2019, 31(01): 188-202.

• Glioma
• EGFRvⅢ expression
• EGFRvⅢ nuclear translocation
• biomarker
• prognosis

Objective: To determine the prognostic implications and clinical significance of epidermal growth factor receptor variant Ⅲ(EGFRvⅢ) expression and EGFRvⅢ nuclear translocation in Chinese human gliomas.Methods: We retrospectively examined EGFRvⅢ expression and EGFRvⅢ nuclear translocation using immunohistochemistry in specimens of 240 Chinese patients with glioma, including 84 World Health Organization(WHO) II gliomas, 84 WHO Ⅲ gliomas and 72 glioblastomas(WHO IV). Factors that correlated with EGFRvⅢ and EGFRvⅢ nuclear translocation expression were analyzed by the Chi-square test. Kaplan-Meier methodology and Cox regression were used for the survival analysis.Results: Log-rank tests showed that patient age, Karnofsky performance scale(KPS) score, tumor grade,EGFRvⅢ expression, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, isocitrate dehydrogenase(IDH)mutation, Ki-67 labeling index and O6-methylguanine-DNA methyltransferase(MGMT) status(P<0.05) were significantly correlated with overall survival(OS) time. Multivariate Cox regression analysis revealed that patient age, tumor grade, EGFRvⅢ nuclear translocation, 1 p/19 q codeletion, and IDH mutation(P<0.05) were significantly correlated with OS. Patients with a high level of EGFRvⅢ nuclear translocation(≥7%) had both significantly shorter OS [hazard ratio(HR): 1.920, 95% confidence interval(95% CI): 1.228-3.003, P=0.004] and progression-free survival(PFS) times(HR: 1.661, 95% CI: 1.116-2.471, P=0.012) than those with a low level of EGFRvⅢ nuclear translocation(<7%).Conclusions: A high level of EGFRvⅢ nuclear translocation in glioma is an independent factor indicating a poor prognosis, but EGFRvⅢ expression is not an independent clinical prognostic factor. The level of EGFRvⅢ nuclear translocation maybe a novel and crucial prognostic biomarker in glioma.

• 单位
  北京大学; 北京大学第三医院