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Br J Cancer. 2014 Feb 18;110(4):1045-52. doi: 10.1038/bjc.2013.794. Epub 2014 Jan 14.

Triple negative breast carcinoma EGFR amplification is not associated with EGFR, Kras or ALK mutations.

Author information

1
1] Department of Pathology, AP-HM CHU Nord, Marseille, France [2] Aix-Marseille Université (AMU), 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, Marseille, France [3] INSERM U 1068 Stress Cellulaire, Campus de Luminy, Case 915, 13009, Marseille, France.
2
Department of Pathology, AP-HM CHU Nord, Marseille, France.
3
UMR 911 Centre de Recherche en Oncologie Biologique et Oncopharmacologie, Faculté de Médecine Timone, Marseille, France.
4
1] Aix-Marseille Université (AMU), 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, Marseille, France [2] Department of Gynaecologic Oncology, AP-HM, CHU Nord, Marseille, France.
5
INSERM U 1068 Stress Cellulaire, Campus de Luminy, Case 915, 13009, Marseille, France.

Abstract

BACKGROUND:

The amplification of epidermal growth factor receptor (EGFR) in triple negative breast carcinomas (TNBC) suggests its potential therapeutic application, as for HER-2, using standardised methods of measurement. In this regard, we aimed to compare several methods for evaluating EGFR amplification along with potential mutations for suitability in clinical practice.

METHODS:

Tissue sections of 138 TNBCs were used (1) to compare EGFR amplification and expression by silver in situ hybridisation (SISH) to qPCR and immunohistochemistry (IHC) and (2) to search for EGFR mutations, along with Kras, PI3K, Braf and HER-2 mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation.

RESULTS:

(1) Amplification of EGFR was observed in well-characterised TNBCs (up to 92%); (2) qPCR correlated with SISH with 94% specificity and 75.6% sensitivity; (3) IHC correlated with SISH with 97% sensitivity and 78% specificity; (4) no EGFR, Kras mutations or EML4-ALK translocations were found, but PI3K and Braf mutations were observed in 26% of cases; and (5) small, acentric circular extrachromosomal DNA similar to 'double minutes' in glioblastomas was observed in 18% of SISH sections.

CONCLUSIONS:

SISH and IHC are methods that are suitable in clinical practice to screen for EGFR amplification and overexpression, which are frequently observed in TNBC. Patients with TNBC are potential candidates for EGFR-targeted therapy combined with PI3K and Braf inhibitors.

PMID:
24423920
PMCID:
PMC3929875
DOI:
10.1038/bjc.2013.794
[Indexed for MEDLINE]
Free PMC Article
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