PMID- 14583498 OWN - NLM STAT- MEDLINE DCOM- 20031222 LR - 20220408 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 63 IP - 20 DP - 2003 Oct 15 TI - Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. PG - 6962-70 AB - Glioblastoma multiforme (GBM) frequently involves amplification and alteration of the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of varied mutations, including the most common mutation, EGFRvIII, as well as wild-type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively analyzed the relationship between treatment outcomes and the EGFR gene in 87 newly diagnosed adult patients with supratentorial GBM enrolled in clinical trials. The EGFR gene status was assessed by Southern blots and EGFR expression by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR, EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in 40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed. On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no EGFR overexpression was present. There was a close correlation between EGFR amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in 27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P < 0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR amplification was an independent, significant, unfavorable predictor for overall survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the relationship of age to EGFR prognostication, the EGFR gene status was a more significant prognosticator in younger patients, particularly in those <60 years (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII overexpression, on the other hand, was not predictive for OS. However, in patients with EGFR amplification, multivariate analysis revealed that EGFRvIII overexpression was an independent, significant, poor prognostic factor for OS (P = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the presence of EGFR amplification is the strongest indicator of a poor survival prognosis. In GBM patients, EGFR is of significant prognostic value for predicting survival, and the overexpression of EGFRvIII with amplification plays an important role in enhanced tumorigenicity. FAU - Shinojima, Naoki AU - Shinojima N AD - Departments of Neurosurgery, Kumamoto University School of Medicine, Kumamoto 860-8556 and 860-0811, Japan. 008m9020@med.stud.kumamoto-u.ac.jp FAU - Tada, Kenji AU - Tada K FAU - Shiraishi, Shoji AU - Shiraishi S FAU - Kamiryo, Takanori AU - Kamiryo T FAU - Kochi, Masato AU - Kochi M FAU - Nakamura, Hideo AU - Nakamura H FAU - Makino, Keishi AU - Makino K FAU - Saya, Hideyuki AU - Saya H FAU - Hirano, Hirofumi AU - Hirano H FAU - Kuratsu, Jun-Ichi AU - Kuratsu J FAU - Oka, Koji AU - Oka K FAU - Ishimaru, Yasuji AU - Ishimaru Y FAU - Ushio, Yukitaka AU - Ushio Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (epidermal growth factor receptor VIII) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antibody Specificity MH - ErbB Receptors/*biosynthesis/genetics/immunology MH - Female MH - Gene Amplification MH - Genes, erbB-1/genetics MH - Glioblastoma/genetics/*metabolism/pathology MH - Humans MH - Immunohistochemistry MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Prognosis MH - Survival Rate EDAT- 2003/10/30 05:00 MHDA- 2003/12/23 05:00 CRDT- 2003/10/30 05:00 PHST- 2003/10/30 05:00 [pubmed] PHST- 2003/12/23 05:00 [medline] PHST- 2003/10/30 05:00 [entrez] PST - ppublish SO - Cancer Res. 2003 Oct 15;63(20):6962-70.