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

• Published in: British journal of cancer Vol. 110; no. 4; pp. 1045 - 1052
• Main Authors: Secq, V, Villeret, J, Fina, F, Carmassi, M, Carcopino, X, Garcia, S, Metellus, I, Boubli, L, Iovanna, J, Charpin, C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.02.2014; Nature Publishing Group
• Subjects: 631/1647/1513; 631/208/2489/1512; 631/208/737; 692/699/67/1347; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cancer therapies; Cell Cycle Proteins - genetics; Clinical medicine; DNA, Circular - genetics; DNA, Circular - isolation & purification; Drug Resistance; Epidemiology; Epidermal growth factor; Female; Gene Amplification; Gynecology. Andrology. Obstetrics; Humans; Kinases; Mammary gland diseases; Medical sciences; Metastasis; Microtubule-Associated Proteins - genetics; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Oncology; Pathology; Phosphatidylinositol 3-Kinases - genetics; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Receptor Protein-Tyrosine Kinases - genetics; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - genetics; Serine Endopeptidases - genetics; Translocation, Genetic; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Tumors; France; amplification mutation; triple negative breast cancer; Breast disease; Enzyme; Transferases; Braf; Malignant tumor; Epidermal growth factor receptor; 1-Phosphatidylinositol 3-kinase; Amplification; K ras Gene; Mammary gland diseases; BRAF Gene; Association; Cancerology; PI3K; C-Onc gene; Genetics; Mutation; Anaplastic lymphoma kinase; EGFR amplification mutation; Protooncogene; Triple negative breast cancer; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.794

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.