Predominant Expression of Mutant EGFR (EGFRvIII) is Rare in Primary Glioblastomas

EGFR amplification is a frequent genetic alteration in primary (de novo) glioblastomas, and is often associated with structural alterations. Most common is variant III (EGFRvIII), which results from a non‐random 801 bp in‐frame deletion of exons 2 to 7 of the EGFR gene. We assessed amplification and...

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Veröffentlicht in:Brain pathology (Zurich, Switzerland) Switzerland), 2004-04, Vol.14 (2), p.131-136
Hauptverfasser: Biernat, Wojciech, Huang, Hervé, Yokoo, Hideaki, Kleihues, Paul, Ohgaki, Hiroko
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Huang, Hervé
Yokoo, Hideaki
Kleihues, Paul
Ohgaki, Hiroko
description EGFR amplification is a frequent genetic alteration in primary (de novo) glioblastomas, and is often associated with structural alterations. Most common is variant III (EGFRvIII), which results from a non‐random 801 bp in‐frame deletion of exons 2 to 7 of the EGFR gene. We assessed amplification and overexpression of EGFRvIII and wild‐type EGFR in 30 glioblastoma biopsies. Immunohistochemically, EGFR overexpression was observed in 20 (67%) of 30 glioblastomas. Eight (27%) cases also showed immunoreactivity to an EGFRvIII antibody. In 6 of these cases, the pattern of EGFR and EGFRvIII overexpression was compared in serial sections: In 4 cases, areas with immunoreactivity to EGFRvIII largely coincided with wild‐type EGFR expression. In the other 2 cases, the areas immunoreactive to EGFRvIII were significantly less extensive than EGFR‐positive areas. To assess whether EGFRvIII is predominantly amplified in tumors with concurrent wild‐type EGFR amplification, we carried out real‐time quantitative PCR using 2 sets of primers located in exon 2 and intron 15 of the EGFR gene. A>5‐fold ratio of relative copy numbers between intron 15 (present both in wild‐type EGFR and EGFRvIII) and exon 2 (present only in wild‐type EGFR, but missing in EGFRvIII) suggested predominant amplification of EGFRvIII in only 3 (10%) of 30 glioblastomas. The observation that intratumoral wild‐type EGFR overexpression is often more extensive and that predominant amplification of EGFRvIII is a rare event would limit the effectiveness of therapeutic approaches based on selective targeting of EGFRvIII.
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Most common is variant III (EGFRvIII), which results from a non‐random 801 bp in‐frame deletion of exons 2 to 7 of the EGFR gene. We assessed amplification and overexpression of EGFRvIII and wild‐type EGFR in 30 glioblastoma biopsies. Immunohistochemically, EGFR overexpression was observed in 20 (67%) of 30 glioblastomas. Eight (27%) cases also showed immunoreactivity to an EGFRvIII antibody. In 6 of these cases, the pattern of EGFR and EGFRvIII overexpression was compared in serial sections: In 4 cases, areas with immunoreactivity to EGFRvIII largely coincided with wild‐type EGFR expression. In the other 2 cases, the areas immunoreactive to EGFRvIII were significantly less extensive than EGFR‐positive areas. To assess whether EGFRvIII is predominantly amplified in tumors with concurrent wild‐type EGFR amplification, we carried out real‐time quantitative PCR using 2 sets of primers located in exon 2 and intron 15 of the EGFR gene. A&gt;5‐fold ratio of relative copy numbers between intron 15 (present both in wild‐type EGFR and EGFRvIII) and exon 2 (present only in wild‐type EGFR, but missing in EGFRvIII) suggested predominant amplification of EGFRvIII in only 3 (10%) of 30 glioblastomas. 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subjects Adult
Aged
Brain Neoplasms - genetics
Female
Gene Amplification
Glioblastoma - genetics
Humans
Image Processing, Computer-Assisted
Immunohistochemistry
Male
Middle Aged
Mutation
Receptor, Epidermal Growth Factor - genetics
Reverse Transcriptase Polymerase Chain Reaction
title Predominant Expression of Mutant EGFR (EGFRvIII) is Rare in Primary Glioblastomas
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