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Updated: Aug 15, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Distinct molecular signature of inflammatory breast cancer by cDNA microarray analysis
Steven Van Laere1, Ilse Van der Auwera, Gert G Van den Eynden
1Translational Cancer Research Group, Lab Pathology, University of Antwerp/University Hospital Antwerp, Edegem and General Hospital, Sint-Augustinus, Wilrijk, Belgium.
Abstract:
Inflammatory breast cancer (IBC) is a clinically distinct and aggressive form of locally advanced breast cancer with largely unknown genetic determinants. Overexpression of the RhoC GTPase and of HER2, and decreased ER-expression are involved in IBC. Multimodality treatment has increased survival but prognosis is still poor. Novel molecular targets for improved neoadjuvant treatment are necessary. Using cDNA microarrays, we performed genome-wide expression profiling of pre-treatment tumour samples of 16 patients with IBC and 18 patients with non-stage-matched non-IBC. Rigid clinical diagnostic criteria according to the TNM classification of the American Joint Committee on Cancer were adopted. Unsupervised hierarchical clustering accurately distinguished IBC and non-IBC samples. A set of 50 discriminator genes was identified in a learning group of tumour samples and was successful in diagnosing IBC in a validation group of samples (accuracy of 88%). Exclusion of ER-related or HER2-related genes did not alter this discriminatory accuracy, indicating that the expression of other genes in addition to ER and HER2 characterize the IBC phenotype. The molecular signature of IBC revealed the overexpression of a large number of NF-kappaB target genes, explaining at least part of the aggressive nature of IBC. Successful validation of some of the overexpressed genes by immunohistochemistry or real-time quantitative PCR demonstrated the robustness of the cDNA microarray experiments. The results of our study provide potential targets for the treatment of patients with IBC.
Insights
Inflammatory breast cancer (IBC) has a unique molecular signature beyond known markers like ER and HER2. This signature, involving NF-kappaB target genes, offers potential new therapeutic targets for this aggressive cancer.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Inflammatory breast cancer (IBC) is an aggressive, locally advanced breast cancer with poor prognosis.
- Known genetic factors include RhoC GTPase overexpression, HER2 overexpression, and decreased estrogen receptor (ER) expression.
- Improved neoadjuvant treatments require novel molecular targets.
Purpose of the Study:
- To identify novel molecular targets for Inflammatory breast cancer (IBC) by performing genome-wide expression profiling.
- To distinguish IBC from non-IBC using gene expression patterns.
- To understand the molecular basis of IBC's aggressive nature.
Main Methods:
- Genome-wide expression profiling using cDNA microarrays on pre-treatment tumor samples from IBC and non-IBC patients.
- Unsupervised hierarchical clustering to differentiate IBC and non-IBC samples.
- Identification and validation of a 50-gene discriminator set for IBC diagnosis.
Main Results:
- Hierarchical clustering accurately distinguished IBC from non-IBC samples.
- A set of 50 discriminator genes achieved 88% accuracy in diagnosing IBC in a validation group.
- The molecular signature of IBC revealed overexpression of numerous NF-kappaB target genes, independent of ER or HER2 status.
- Validation of gene expression using immunohistochemistry and real-time quantitative PCR confirmed microarray findings.
Conclusions:
- The gene expression profile of IBC is characterized by a distinct set of genes beyond ER and HER2.
- Overexpression of NF-kappaB target genes contributes to the aggressive phenotype of IBC.
- These findings provide potential novel molecular targets for the neoadjuvant treatment of IBC patients.
