Targeting EGFR in bladder cancer

G. J. Villares, M. Zigler, K. Blehm, C. Bogdan, D. McConkey, D. Colin, Menashe Bar-Eli

Research output: Contribution to journalArticle

Abstract

Expression and overexpression of the epidermal growth factor receptor (EGFR) have been described in several solid tumors including bladder, breast, colorectal, NSCLC, prostate, and ovarian cancers. In addition to gene amplification, point mutations within the kinase domain also occur. Previous reports indicate that the patient's response to gefitinib depends on either the presence of mutations within the kinase domain of EGFR or the expression of the most frequent alteration, the truncated EGFR variant III (EGFRvIII). Therefore, it is important to determine if these EGFR alterations are present in urothelial carcinoma. The kinase domain of EGFR (exons 18-21) from 11 bladder cancer cell lines as well as from 75 patient tumors was analyzed by automated sequencing. No mutations were detected in all samples tested. Furthermore, analysis of EGFRvIII by immunohistochemistry revealed that almost half of all the patient samples expressed this truncation in a urothelial carcinoma tissue microarray. However, there have been previous reports of inconsistencies in detecting EGFRvIII by immunohistochemistry owing to the specificity of the antibodies and the methodologies utilized. Therefore, these results were validated by reverse transcription PCR, real-time PCR and western blot analysis. In these assays, none of the samples tested positive for EGFRvIII. Taken together, these results indicate that mutations within the tyrosine kinase domain of EGFR and expression of EGFRvIII are rare events in bladder cancer and therefore do not contribute to the malignant phenotype of this tumor. These results have clinical implications in selecting tyrosine kinase inhibitors for the therapy of urothelial carcinoma.

Original languageEnglish (US)
Pages (from-to)573-579
Number of pages7
JournalWorld journal of urology
Volume25
Issue number6
DOIs
StatePublished - Dec 2007
Externally publishedYes

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Keywords

  • Bladder cancer
  • EGFR
  • Mutations
  • Tyrosine kinase

ASJC Scopus subject areas

  • Urology

Cite this

Villares, G. J., Zigler, M., Blehm, K., Bogdan, C., McConkey, D., Colin, D., & Bar-Eli, M. (2007). Targeting EGFR in bladder cancer. World journal of urology, 25(6), 573-579. https://doi.org/10.1007/s00345-007-0202-7