Ano de Publicação: 2012
AUTORIA
Alcides Chaux, MDa, Julie S. Cohen, ScM, CGCb, Luciana Schultz, MDa, Roula Albadine,
MDa, Sana Jadallah, MDa, Kathleen M. Murphy, PhDc, Rajni Sharma, PhDa, Mark P.
Schoenberg, MDd, and George J. Netto, MDa,d,e,*
aDepartment of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
bKennedy Krieger Institute, Baltimore, MD 21205, USA
cProPath, Dallas, TX 75247, USA
dDepartment of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
eDepartment of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
RESUMO
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.