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

V Secq1, J Villeret2, F Fina3

  • 11] 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.

British Journal of Cancer
|January 16, 2014
PubMed
Abstract

Insights

Epidermal growth factor receptor (EGFR) amplification is common in triple-negative breast cancer (TNBC). Silver in situ hybridization (SISH) and immunohistochemistry (IHC) are suitable clinical methods for screening, suggesting TNBC patients may benefit from targeted therapies.

Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genetics

Background:

  • Epidermal growth factor receptor (EGFR) amplification is prevalent in triple-negative breast cancer (TNBC).
  • Standardized measurement methods are needed to assess EGFR amplification for potential therapeutic targeting in TNBC.
  • This study evaluated various methods for detecting EGFR amplification and mutations in TNBC.

Purpose of the Study:

  • To compare silver in situ hybridization (SISH), quantitative polymerase chain reaction (qPCR), and immunohistochemistry (IHC) for evaluating EGFR amplification in TNBC.
  • To investigate the presence of mutations in EGFR, Kras, PI3K, Braf, and HER-2, as well as EML4-ALK translocations in TNBC.
  • To assess the clinical suitability of different diagnostic methods for EGFR alterations in TNBC.

Main Methods:

  • 138 TNBC tissue sections were analyzed.
  • EGFR amplification and expression were compared using SISH, qPCR, and IHC.
  • Mutation analysis included EGFR, Kras, PI3K, Braf, HER-2, and EML4-ALK translocation detection.

Main Results:

  • EGFR amplification was detected in up to 92% of TNBC cases.
  • qPCR showed 94% specificity and 75.6% sensitivity compared to SISH.
  • IHC demonstrated 97% sensitivity and 78% specificity relative to SISH.
  • PI3K and Braf mutations occurred in 26% of cases; no EGFR mutations or EML4-ALK translocations were found.
  • Extrachromosomal DNA resembling 'double minutes' was observed in 18% of SISH sections.

Conclusions:

  • SISH and IHC are clinically viable methods for screening EGFR amplification and overexpression in TNBC.
  • Frequent EGFR amplification and overexpression in TNBC suggest potential for EGFR-targeted therapies.
  • TNBC patients may benefit from combination therapies including EGFR, PI3K, and Braf inhibitors.

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