Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma

Christopher E. Pelloski, Karla V. Ballman, Alfred F. Furth, Li Zhang, E. Lin, Erik P. Sulman, Krishna Bhat, J. Matthew McDonald, W. K Alfred Yung, Howard Colman, Shiao Y. Woo, Amy B. Heimberger, Dima Suki, Michael D. Prados, Susan M. Chang, Fred G. Barker, Jan Craig Buckner, C. David James, Kenneth Aldape

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Abstract

Purpose: The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the clinical significance of GBM subtypes as defined by EGFRvIII status. Patients and Methods: The expression of EGFRvIII was assessed by immunohistochemistry in 649 patients with newly diagnosed GBM. These data were then examined in conjunction with the expression of phospho-intermediates (in a subset of these patients) of downstream AKT and Ras pathways and YKL-40 as well as with known clinical risk factors, including the Radiation Therapy Oncology Group's recursive partitioning analysis (RTOG-RPA) class. Results: The RTOG-RPA class was highly predictive of survival in EGFRvIII-negative patients but much less predictive in EGFRvIII-positive patients. These findings were seen in both an initial test set (n = 268) and a larger validation set (n = 381). Similarly, activation of the AKT/MAPK pathways and YKL-40 positivity were predictive of poor outcome in EGFRvIII-negative patients but not in EGFRvIII-positive patients. Pair-wise combinations of markers identified EGFRvIII and YKL-40 as prognostically important. In particular, outcome in patients with EGFRvIII-negative/YKL-40-negative tumors was significantly better than the outcome in patients with the other three combinations of these two markers. Conclusion: Established prognostic factors in GBM were not predictive of outcome in the EGFRvIII-positive subset, although this requires confirmation in independent data sets. GBMs negative for both EGFRvIII and YKL-40 show less aggressive behavior.

Original languageEnglish (US)
Pages (from-to)2288-2294
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number16
DOIs
StatePublished - Jun 1 2007

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Glioblastoma
Epidermal Growth Factor Receptor
Radiation Oncology
Radiotherapy
Immunohistochemistry
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Pelloski, C. E., Ballman, K. V., Furth, A. F., Zhang, L., Lin, E., Sulman, E. P., ... Aldape, K. (2007). Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. Journal of Clinical Oncology, 25(16), 2288-2294. https://doi.org/10.1200/JCO.2006.08.0705

Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. / Pelloski, Christopher E.; Ballman, Karla V.; Furth, Alfred F.; Zhang, Li; Lin, E.; Sulman, Erik P.; Bhat, Krishna; McDonald, J. Matthew; Yung, W. K Alfred; Colman, Howard; Woo, Shiao Y.; Heimberger, Amy B.; Suki, Dima; Prados, Michael D.; Chang, Susan M.; Barker, Fred G.; Buckner, Jan Craig; James, C. David; Aldape, Kenneth.

In: Journal of Clinical Oncology, Vol. 25, No. 16, 01.06.2007, p. 2288-2294.

Research output: Contribution to journalArticle

Pelloski, CE, Ballman, KV, Furth, AF, Zhang, L, Lin, E, Sulman, EP, Bhat, K, McDonald, JM, Yung, WKA, Colman, H, Woo, SY, Heimberger, AB, Suki, D, Prados, MD, Chang, SM, Barker, FG, Buckner, JC, James, CD & Aldape, K 2007, 'Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma', Journal of Clinical Oncology, vol. 25, no. 16, pp. 2288-2294. https://doi.org/10.1200/JCO.2006.08.0705
Pelloski, Christopher E. ; Ballman, Karla V. ; Furth, Alfred F. ; Zhang, Li ; Lin, E. ; Sulman, Erik P. ; Bhat, Krishna ; McDonald, J. Matthew ; Yung, W. K Alfred ; Colman, Howard ; Woo, Shiao Y. ; Heimberger, Amy B. ; Suki, Dima ; Prados, Michael D. ; Chang, Susan M. ; Barker, Fred G. ; Buckner, Jan Craig ; James, C. David ; Aldape, Kenneth. / Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 16. pp. 2288-2294.
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abstract = "Purpose: The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the clinical significance of GBM subtypes as defined by EGFRvIII status. Patients and Methods: The expression of EGFRvIII was assessed by immunohistochemistry in 649 patients with newly diagnosed GBM. These data were then examined in conjunction with the expression of phospho-intermediates (in a subset of these patients) of downstream AKT and Ras pathways and YKL-40 as well as with known clinical risk factors, including the Radiation Therapy Oncology Group's recursive partitioning analysis (RTOG-RPA) class. Results: The RTOG-RPA class was highly predictive of survival in EGFRvIII-negative patients but much less predictive in EGFRvIII-positive patients. These findings were seen in both an initial test set (n = 268) and a larger validation set (n = 381). Similarly, activation of the AKT/MAPK pathways and YKL-40 positivity were predictive of poor outcome in EGFRvIII-negative patients but not in EGFRvIII-positive patients. Pair-wise combinations of markers identified EGFRvIII and YKL-40 as prognostically important. In particular, outcome in patients with EGFRvIII-negative/YKL-40-negative tumors was significantly better than the outcome in patients with the other three combinations of these two markers. Conclusion: Established prognostic factors in GBM were not predictive of outcome in the EGFRvIII-positive subset, although this requires confirmation in independent data sets. GBMs negative for both EGFRvIII and YKL-40 show less aggressive behavior.",
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AU - Ballman, Karla V.

AU - Furth, Alfred F.

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AU - Sulman, Erik P.

AU - Bhat, Krishna

AU - McDonald, J. Matthew

AU - Yung, W. K Alfred

AU - Colman, Howard

AU - Woo, Shiao Y.

AU - Heimberger, Amy B.

AU - Suki, Dima

AU - Prados, Michael D.

AU - Chang, Susan M.

AU - Barker, Fred G.

AU - Buckner, Jan Craig

AU - James, C. David

AU - Aldape, Kenneth

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N2 - Purpose: The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the clinical significance of GBM subtypes as defined by EGFRvIII status. Patients and Methods: The expression of EGFRvIII was assessed by immunohistochemistry in 649 patients with newly diagnosed GBM. These data were then examined in conjunction with the expression of phospho-intermediates (in a subset of these patients) of downstream AKT and Ras pathways and YKL-40 as well as with known clinical risk factors, including the Radiation Therapy Oncology Group's recursive partitioning analysis (RTOG-RPA) class. Results: The RTOG-RPA class was highly predictive of survival in EGFRvIII-negative patients but much less predictive in EGFRvIII-positive patients. These findings were seen in both an initial test set (n = 268) and a larger validation set (n = 381). Similarly, activation of the AKT/MAPK pathways and YKL-40 positivity were predictive of poor outcome in EGFRvIII-negative patients but not in EGFRvIII-positive patients. Pair-wise combinations of markers identified EGFRvIII and YKL-40 as prognostically important. In particular, outcome in patients with EGFRvIII-negative/YKL-40-negative tumors was significantly better than the outcome in patients with the other three combinations of these two markers. Conclusion: Established prognostic factors in GBM were not predictive of outcome in the EGFRvIII-positive subset, although this requires confirmation in independent data sets. GBMs negative for both EGFRvIII and YKL-40 show less aggressive behavior.

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