EGFR Over-Expression, Genetic Heterogeneity and Mutation in Triple Negative Breast Carcinomas.
Amir Behdad, Jean Lopategui, Shikha Bose. Cedar-Sinai Medical Center, Los Angeles, CA
Background: EGFR is a growth factor receptor that is activated in many cancers. Several agents targeting EGFR are in advanced clinical development for treatment of various human cancers notably lung, colon and head and neck. Triple negative breast carcinomas (TNBCA) are an aggressive but heterogeneous group of tumors characterized by a lack of well-defined targeted therapies. A subgroup of these tumors has been shown to overexpress EGFR thus raising the feasibility of targeted therapy. This study is designed to systematically evaluate the over-expression, amplification and mutation of EGFR in TNBCA, and determine its relation to conventional prognostic factors.
Design: 25 cases of TNBCA diagnosed between 2009-2010 were randomly selected from our files. Cases were evaluated for EGFR expression by immunohistochemistary (IHC), amplification by FISH using the EGFR and CEP 7 probes and mutations on exon 19 and 21 by PCR. Results were correlated with various prognostic factors including tumor size, lymph node metastasis, TNM stage and proliferation index (Ki-67 expression).
Results: 13 (52%) cases showed EGFR overexpression by IHC as demonstrated by partial/complete membrane staining in 5 to 80% (median 25.8%) of tumor cells. Significant heterogeneity was noted in expression in different areas of the tumor. No correlation was observed between IHC results and various prognostic factors. 17 (68%) cases demonstrated intra-tumoral genetic heterogeneity for EGFR amplification (ITGHEA), including 13 (52%) cases with more than 6 EGFR copies per cell in 2.5 to 37.5% of carcinoma cells and 4 (16%) cases with EGFR/CEP7 ratio of more than 2.2 in 2.5 to 12.5 % of tumor cells. Cases with ITGHEA did not correlate with any of the prognostic markers with the exception of Ki67. Tumors with ITGHEA tended to show higher rates of proliferation than those without it (p=0.02). FISH results did not correlate with IHC results. No EGFR mutations were identified.
Conclusions: 1. Triple negative breast carcinomas demonstrated EGFR overexpression and intratumoral genetic heterogeneity for EGFR amplification in a significant proportion of cases. 2. Intratumoral genetic heterogeneity for EGFR amplification correlated significantly with proliferation index. 3. No correlation was observed between EGFR over expression and intratumoral genetic heterogeneity for EGFR amplification. 4. Additional studies are warranted to determine the role of EGFR overexpression and intratumoral genetic heterogeneity for EGFR amplification in the selection of patients for targeted therapy.
Monday, February 28, 2011 1:00 PM
Poster Session II # 66, Monday Afternoon