title: 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.
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.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.forename: Julie S
authors.initials: JS
authors.lastname: Cohen
authors.forename: Luciana
authors.initials: L
authors.lastname: Schultz
authors.forename: Roula
authors.initials: R
authors.lastname: Albadine
authors.forename: Sana
authors.initials: S
authors.lastname: Jadallah
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Mark P
authors.initials: MP
authors.lastname: Schoenberg
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
mesh_terms: D000368:Aged; D018070:Biological Specimen Banks; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016612:Paraffin Embedding; D016707:Tissue Fixation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005557:Formaldehyde; C512478:EGFR protein, human; D066246:ErbB Receptors