High epidermal growth factor receptor immunohistochemical expression in urothelial carcinoma of the bladder is not associated with EGFR mutations in exons 19 and 21

A study using formalin-fixed, paraffin-embedded archival tissues

Alcides Chaux, Julie S. Cohen, Luciana Schultz, Roula Albadine, Sana Jadallah, Kathleen M. Murphy, Rajni Sharma, Mark P. Schoenberg, George J. Netto

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine kinase family reported to be overexpressed in a variety of solid malignancies. Mutations in exons 19 to 21 of the tyrosine kinase domain have been detected in a subset of these tumors and its presence associated with a better response to EGFR inhibitors. Several clinical trials are currently underway to evaluate the performance of such drugs in patients with bladder cancer, but data on EGFR mutation status are limited. The current study assesses EGFR immunohistochemical expression and the presence of mutations in exons 19 and 21 by polymerase chain reaction in 19 bladder urothelial carcinomas from formalin-fixed, paraffin-embedded tissues. Representative paraffin sections were microdissected for DNA extraction using a pinpoint isolation system. Parallel sections were immunostained using a monoclonal anti-EGFR antibody. No mutations in exons 19 and 21 of EGFR were identified in any of the cases. Immunohistochemical EGFR positivity was observed in 14 of 19 cases. In summary, we found EGFR protein expression in 74% of urothelial carcinomas, but we failed to detect EGFR mutations at exons 19 to 21, suggesting that EGFR overexpression is not related to the presence of mutations in the tyrosine kinase domain of the gene. Mutation analysis of EGFR exons 19 and 21 is feasible in microdissected paraffin sections from archival tissues. Immunohistochemical expression of EGFR may not be useful to predict therapeutic response to EGFR inhibitors in patients with urothelial carcinomas. To explain EGFR immunohistochemical overexpression, other mechanisms besides mutations in the EGFR kinase domain should be investigated in future studies.

Original languageEnglish (US)
Pages (from-to)1590-1595
Number of pages6
JournalHuman Pathology
Volume43
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Paraffin
Formaldehyde
Exons
Urinary Bladder
Carcinoma
Mutation
Protein-Tyrosine Kinases
Urinary Bladder Neoplasms
Neoplasms

Keywords

  • EGFR expression
  • EGFR mutation
  • Exon 19 deletion
  • Exon 21 L858R substitution
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

High epidermal growth factor receptor immunohistochemical expression in urothelial carcinoma of the bladder is not associated with EGFR mutations in exons 19 and 21 : A study using formalin-fixed, paraffin-embedded archival tissues. / Chaux, Alcides; Cohen, Julie S.; Schultz, Luciana; Albadine, Roula; Jadallah, Sana; Murphy, Kathleen M.; Sharma, Rajni; Schoenberg, Mark P.; Netto, George J.

In: Human Pathology, Vol. 43, No. 10, 10.2012, p. 1590-1595.

Research output: Contribution to journalArticle

Chaux, Alcides ; Cohen, Julie S. ; Schultz, Luciana ; Albadine, Roula ; Jadallah, Sana ; Murphy, Kathleen M. ; Sharma, Rajni ; Schoenberg, Mark P. ; Netto, George J. / High epidermal growth factor receptor immunohistochemical expression in urothelial carcinoma of the bladder is not associated with EGFR mutations in exons 19 and 21 : A study using formalin-fixed, paraffin-embedded archival tissues. In: Human Pathology. 2012 ; Vol. 43, No. 10. pp. 1590-1595.
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abstract = "Epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine kinase family reported to be overexpressed in a variety of solid malignancies. Mutations in exons 19 to 21 of the tyrosine kinase domain have been detected in a subset of these tumors and its presence associated with a better response to EGFR inhibitors. Several clinical trials are currently underway to evaluate the performance of such drugs in patients with bladder cancer, but data on EGFR mutation status are limited. The current study assesses EGFR immunohistochemical expression and the presence of mutations in exons 19 and 21 by polymerase chain reaction in 19 bladder urothelial carcinomas from formalin-fixed, paraffin-embedded tissues. Representative paraffin sections were microdissected for DNA extraction using a pinpoint isolation system. Parallel sections were immunostained using a monoclonal anti-EGFR antibody. No mutations in exons 19 and 21 of EGFR were identified in any of the cases. Immunohistochemical EGFR positivity was observed in 14 of 19 cases. In summary, we found EGFR protein expression in 74{\%} of urothelial carcinomas, but we failed to detect EGFR mutations at exons 19 to 21, suggesting that EGFR overexpression is not related to the presence of mutations in the tyrosine kinase domain of the gene. Mutation analysis of EGFR exons 19 and 21 is feasible in microdissected paraffin sections from archival tissues. Immunohistochemical expression of EGFR may not be useful to predict therapeutic response to EGFR inhibitors in patients with urothelial carcinomas. To explain EGFR immunohistochemical overexpression, other mechanisms besides mutations in the EGFR kinase domain should be investigated in future studies.",
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