Heimberger Amy B, Hlatky Roman, Suki Dima, Yang David, Weinberg Jeff, Gilbert Mark, Sawaya Raymond, Aldape Kenneth
Department of Neurosurgery, University of Texas M.D. Anderson Cancer Center, Unit 442, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Clin Cancer Res. 2005 Feb 15;11(4):1462-6. doi: 10.1158/1078-0432.CCR-04-1737.
The epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% to 60% of glioblastoma multiforme tumors, and the most common EGFR mutant, EGFRvIII, is expressed in 24% to 67% of cases. We sought to determine whether glioblastoma multiforme expression of either overexpressed wild-type EGFR or the mutant EGFRvIII is an independent predictor of overall patient survival.
Glioblastoma multiforme patients (n = 196) underwent a > or =95% volumetric tumor resection followed by conformal radiation. Their EGFR and EGFRvIII status was determined by immunohistochemistry and survival analyses were done.
In our study of glioblastoma multiforme patients, 46% (n = 91) failed to express EGFR, 54% (n = 105) had overexpression of the wild-type EGFR, and 31% (n = 61) also expressed the EGFRvIII. Patients within groups expressing the EGFR, EGFRvIII, or lacking EGFR expression did not differ in age, sex, Karnofsky performance scale score, extent of tumor resection, or radiation. The median overall survival times for patients with tumors having EGFR expression absent, overexpressed only, or mutant (EGFRvIII) were 0.96, 0.98, and 1.07 years, respectively. However, for patients surviving > or =1 year, these values were 2.03, 2.02, and 1.21 years (P < 0.0001; log-rank test comparing EGFRvIII with all others). This effect remained significant in the multivariate analysis after adjustment for all other cofactors including age and Karnofsky performance scale score (rate ratio 4.34; 95% confidence interval, 2.21-8.51).
Neither the overexpressed wild-type EGFR nor EGFRvIII was an independent predictor of median overall survival in this selected cohort of patients who underwent extensive tumor resection. However, in patients surviving > or =1 year, the expression of EGFRvIII was an independent negative prognostic indicator.
表皮生长因子受体(EGFR)在约50%至60%的多形性胶质母细胞瘤中过表达,最常见的EGFR突变体EGFRvIII在24%至67%的病例中表达。我们试图确定多形性胶质母细胞瘤中过表达的野生型EGFR或突变体EGFRvIII的表达是否是患者总体生存的独立预测指标。
多形性胶质母细胞瘤患者(n = 196)接受了≥95%的肿瘤体积切除,随后进行适形放疗。通过免疫组织化学确定他们的EGFR和EGFRvIII状态,并进行生存分析。
在我们对多形性胶质母细胞瘤患者的研究中,46%(n = 91)未表达EGFR,54%(n = 105)野生型EGFR过表达,31%(n = 61)也表达EGFRvIII。在表达EGFR、EGFRvIII或缺乏EGFR表达的组内患者在年龄、性别、卡诺夫斯基功能状态评分、肿瘤切除范围或放疗方面没有差异。肿瘤无EGFR表达、仅过表达或突变(EGFRvIII)的患者的中位总生存时间分别为0.96、0.98和1.07年。然而,对于存活≥1年的患者,这些值分别为2.03、2.02和1.21年(P < 0.0001;对数秩检验比较EGFRvIII与所有其他组)。在对包括年龄和卡诺夫斯基功能状态评分在内的所有其他协变量进行调整后的多变量分析中,这种效应仍然显著(率比4.34;95%置信区间,2.21 - 8.51)。
在这个接受广泛肿瘤切除的特定患者队列中,过表达的野生型EGFR和EGFRvIII均不是中位总生存的独立预测指标。然而,在存活≥1年的患者中,EGFRvIII的表达是一个独立的不良预后指标。