PMID- 17538175 OWN - NLM STAT- MEDLINE DCOM- 20070612 LR - 20220408 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 25 IP - 16 DP - 2007 Jun 1 TI - Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. PG - 2288-94 AB - 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. FAU - Pelloski, Christopher E AU - Pelloski CE AD - Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. FAU - Ballman, Karla V AU - Ballman KV FAU - Furth, Alfred F AU - Furth AF FAU - Zhang, Li AU - Zhang L FAU - Lin, E AU - Lin E FAU - Sulman, Erik P AU - Sulman EP FAU - Bhat, Krishna AU - Bhat K FAU - McDonald, J Matthew AU - McDonald JM FAU - Yung, W K Alfred AU - Yung WK FAU - Colman, Howard AU - Colman H FAU - Woo, Shiao Y AU - Woo SY FAU - Heimberger, Amy B AU - Heimberger AB FAU - Suki, Dima AU - Suki D FAU - Prados, Michael D AU - Prados MD FAU - Chang, Susan M AU - Chang SM FAU - Barker, Fred G 2nd AU - Barker FG 2nd FAU - Buckner, Jan C AU - Buckner JC FAU - James, C David AU - James CD FAU - Aldape, Kenneth AU - Aldape K LA - eng PT - Journal Article PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Adipokines) RN - 0 (CHI3L1 protein, human) RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (Glycoproteins) RN - 0 (Lectins) RN - 0 (epidermal growth factor receptor VIII) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM CIN - Nat Clin Pract Oncol. 2008 Apr;5(4):188-9. PMID: 18319741 MH - Adipokines MH - Chitinase-3-Like Protein 1 MH - ErbB Receptors/*analysis MH - Glioblastoma/*chemistry/classification/mortality MH - Glycoproteins/analysis MH - Humans MH - Lectins MH - Middle Aged MH - Multivariate Analysis MH - Prognosis MH - Regression Analysis EDAT- 2007/06/01 09:00 MHDA- 2007/06/15 09:00 CRDT- 2007/06/01 09:00 PHST- 2007/06/01 09:00 [pubmed] PHST- 2007/06/15 09:00 [medline] PHST- 2007/06/01 09:00 [entrez] AID - 25/16/2288 [pii] AID - 10.1200/JCO.2006.08.0705 [doi] PST - ppublish SO - J Clin Oncol. 2007 Jun 1;25(16):2288-94. doi: 10.1200/JCO.2006.08.0705.