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Updated: Aug 29, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Identification and validation of an ERBB2 gene expression signature in breast cancers
François Bertucci1, Nathalie Borie, Christophe Ginestier
1Département d'Oncologie Moléculaire, Institut Paoli-Calmettes and UMR119 Inserm, IFR57, and Faculté de Médecine, Université de la Méditerranée, Marseille, France.
Abstract:
ERBB2 is a transmembrane tyrosine kinase receptor encoded by a gene located in chromosome region 17q12. Overexpression of ERBB2, generally by way of gene amplification, plays a role in mammary oncogenesis. This alteration can be overcome by use of the humanized monoclonal antibody trastuzumab (Herceptin). Accurate determination of ERBB2 status is required for appropriate use of this targeted therapy and is currently analysed by immunohistochemistry (IHC) on tissue sections and/or fluorescence in situ hybridisation (FISH) on interphase chromosomes. We have studied the gene expression profiles of a series of 213 breast tumours and 16 breast cancer cell lines with known ERBB2 status, using Ipsogen's DiscoveryChip microarrays with approximately 9000 cDNAs. We have identified 36 genes and expressed sequence tags that were differentially expressed in tumours and in cell lines with and without ERBB2 protein overexpression. This ERBB2-specific gene expression signature (GES) contained 29 overexpressed genes including the ERBB2 gene itself, five genes located in its immediate vicinity on 17q12, non-17q genes such as GATA4 and eight downregulated genes including oestrogen receptor alpha (ER). Some correlations were validated at the protein level using IHC on tissue microarrays. The GES was able to distinguish ERBB2-negative and -positive cancer samples, as well as FISH-negative and FISH-positive ERBB2 2+ IHC samples.
Insights
Researchers identified a gene expression signature (GES) that accurately distinguishes ERBB2-positive and -negative breast cancer. This signature aids in determining ERBB2 status for targeted therapy like trastuzumab.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- ERBB2 (Erb-B2 receptor tyrosine kinase 2) gene amplification drives mammary oncogenesis.
- Trastuzumab targets ERBB2-overexpressing breast cancers, necessitating accurate ERBB2 status determination.
- Current ERBB2 testing involves immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
Purpose of the Study:
- To identify a gene expression signature (GES) associated with ERBB2 status in breast cancer.
- To evaluate the potential of this GES for classifying ERBB2-positive and -negative tumors.
- To correlate gene expression findings with protein levels and established diagnostic methods.
Main Methods:
- Gene expression profiling of 213 breast tumors and 16 cell lines using DiscoveryChip microarrays (~9000 cDNAs).
- Analysis of differential gene expression between ERBB2-positive and ERBB2-negative samples.
- Validation of gene expression findings at the protein level using IHC on tissue microarrays.
Main Results:
- A 36-gene ERBB2-specific GES was identified, including ERBB2 and nearby 17q12 genes.
- The GES comprised 29 overexpressed and 8 downregulated genes (e.g., ER).
- The GES accurately differentiated ERBB2-negative/positive and FISH-negative/positive samples.
Conclusions:
- The identified GES serves as a molecular marker for ERBB2 status in breast cancer.
- This gene expression signature can complement or potentially refine existing ERBB2 diagnostic methods.
- The findings support the use of gene expression profiling for classifying breast cancers based on ERBB2 alterations.
