The natural history of EGFR and EGFRvIII in glioblastoma patients

BackgroundThe epidermal growth factor receptor (EGFR) is over expressed in approximately 50–60% of glioblastoma (GBM) tumors, and the most common EGFR mutant, EGFRvIII, is expressed in 24–67% of cases. This study was designed to address whether over expressed EGFR or EGFRvIII is an actual independent prognostic indicator of overall survival in a uniform body of patients in whom gross total surgical resection (GTR; ≥ 95% resection) was not attempted or achieved.MethodsBiopsed or partially/subtotally resected GBM patients (N = 54) underwent adjuvant conformal radiation and chemotherapy. Their EGFR and EGFRvIII status was determined by immunohistochemistry and Kaplan-Meier estimates of overall survival were obtained.ResultsIn our study of GBM patients with less than GTR, 42.6% (n = 23) failed to express EGFR, 25.9% (n = 14) had over expression of the wild-type EGFR only and 31.5 % (n = 17) expressed the EGFRvIII. Patients within groups expressing the EGFR, EGFRvIII, or lacking EGFR expression did not differ in age, Karnofsky Performance Scale (KPS) score, extent of tumor resection. They all had received postoperative radiation and chemotherapy. The median overall survival times for patients with tumors having no EGFR expression, over expressed EGFR only, or EGFRvIII were 12.3 (95% CI, 8.04–16.56), 11.03 (95% CI, 10.18–11.89) and 14.07 (95% CI, 7.39–20.74) months, respectively, log rank test p > 0.05). Patients with tumors that over expressed the EGFR and EGFRvIII were more likely to present with ependymal spread, 21.4% and 35.3% respectively, compared to those patients whose GBM failed to express either marker, 13.0%, although the difference was not statistically significant. There was no significant difference in multifocal disease or gliomatosis cerebri among EGFR expression groups.ConclusionThe over expressed wild-type EGFR and EGFRvIII are not independent predictors of median overall survival in the cohort of patients who did not undergo extensive tumor resection.

[1]  D. Nelson,et al.  Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. , 1993, Journal of the National Cancer Institute.

[2]  P. Kolm,et al.  Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation. , 1996, International journal of radiation oncology, biology, physics.

[3]  R. Sankila,et al.  A population‐based study on the incidence and survival rates of 3857 glioma patients diagnosed from 1953 to 1984 , 1991, Cancer.

[4]  Ochi,et al.  Prognostic significance of Ki67, p53 and epidermal growth factor receptor immunostaining in human glioblastomas , 1998, Neuropathology and applied neurobiology.

[5]  S. Brem,et al.  Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973-1991. , 1998, Journal of neurosurgery.

[6]  Caterina Giannini,et al.  Immunohistochemical Detection of EGFRvIII in High Malignancy Grade Astrocytomas and Evaluation of Prognostic Significance , 2004, Journal of neuropathology and experimental neurology.

[7]  Susan M. Chang,et al.  Glioblastoma Patients Epidermal Growth Factor Receptor , and Survival in Analysis of Complex Relationships between Age , p 53 , Updated , 2001 .

[8]  Douglas C. Miller,et al.  Survival of Patients with Glioblastoma Multiforme is not Influenced by Altered Expression of P16, P53, EGFR, MDM2 or Bcl‐2 Genes , 1998, Brain pathology.

[9]  G Milano,et al.  Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[10]  R. McLendon,et al.  Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. , 1997, Cancer research.

[11]  D.,et al.  Regression Models and Life-Tables , 2022 .

[12]  V. P. Collins,et al.  Functional characterization of an EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGFR gene amplification. , 1994, Oncogene.

[13]  R. Bjerkvig,et al.  Epidermal growth factor and laminin receptors contribute to migratory and invasive properties of gliomas. , 1997, Invasion & metastasis.

[14]  Kenji Tada,et al.  Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. , 2003, Cancer research.

[15]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[16]  J. Cairncross,et al.  Supratentorial anaplastic gliomas in adults. The prognostic importance of extent of resection and prior low-grade glioma. , 1989, Journal of neurosurgery.

[17]  O D Laerum,et al.  Effect of epidermal growth factor on glioma cell growth, migration, and invasion in vitro. , 1990, Cancer research.

[18]  R. Fimmers,et al.  Lack of prognostic relevance of alterations in the epidermal growth factor receptor-transforming growth factor-alpha pathway in human astrocytic gliomas. , 1996, Journal of neurosurgery.

[19]  C. James,et al.  PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. , 2001, Journal of the National Cancer Institute.

[20]  David J. Yang,et al.  Prognostic Effect of Epidermal Growth Factor Receptor and EGFRvIII in Glioblastoma Multiforme Patients , 2005, Clinical Cancer Research.

[21]  P. Kleihues,et al.  Predominant Expression of Mutant EGFR (EGFRvIII) is Rare in Primary Glioblastomas , 2004, Brain pathology.

[22]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[23]  C. James,et al.  Gene amplification as a prognostic factor in primary and secondary high-grade malignant gliomas. , 1998, International journal of oncology.