Expression of constitutively activated EGFRvIII in non-small cell lung cancer

Isamu Okamoto, Lawrence C. Kenyon, David R. Emlet, Takeshi Mori, Ji Ichiro Sasaki, Susumu Hirosako, Yasuko Ichikawa, Hiroto Kishi, Andrew K. Godwin, Masakazu Yoshioka, Moritaka Suga, Mitsuhiro Matsumoto, Albert J. Wong

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)

Abstract

The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvIII, de2-7 EGFR or ΔEGFR) has an in-frame deletion of the extracellular domain and is found in numerous types of human tumors. Since EGFRvIII has been reported to be tumor-specific and has oncogenic potential, it is being investigated as a potential therapeutic target. Because the cell-specific expression of EGFRvIII in lung has not been well documented, we examined the expression of EGFRvIII in 76 non-small cell lung cancers (NSCLCs) and 10 non-neoplastic lung tissues by immunohistochemistry using a new monoclonal antibody specific for this variant receptor. We found a higher incidence (30 of 76, 39%) of enhanced EGFRvIII expression in NSCLC than previously described. Interestingly, the presence of EGFRvIII was also observed in several normal tissue components of lung (e.g., normal bronchial epithelium). Given the high prevalence of EGFRvIII in NSCLC, a newly developed phospho-specific (activated) EGFR antibody was employed for immunohistochemical analysis that permitted visualization of activated EGFR and/or EGFRvIII in tumors. This study presents evidence, for the first time, that EGFRvIII expressed in human tumors is phosphorylated and hence activated. Our results suggest that the sustained activation of EGFRvIII is implicated in the pathogenesis of NSCLC and thus EGFRvIII is a potential therapeutic target in this challenging disease.

Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalCancer Science
Volume94
Issue number1
DOIs
Publication statusPublished - Jan 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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