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Breast Cancer Research and Treatment

, Volume 93, Issue 3, pp 237–246 | Cite as

Distinct Molecular Signature of Inflammatory Breast Cancer by cDNA Microarray Analysis

  • Steven Van Laere
  • Ilse Van der Auwera
  • Gert G. Van den Eynden
  • Stephen B. Fox
  • Fabrizio Bianchi
  • Adrian L. Harris
  • Peter van Dam
  • Eric A. Van Marck
  • Peter B. Vermeulen
  • Luc Y. DirixEmail author
Report

Summary

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-κB 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.

Key words

expression profiling inflammatory breast cancer NF-κB 

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Copyright information

© Springer 2005

Authors and Affiliations

  • Steven Van Laere
    • 1
  • Ilse Van der Auwera
    • 1
  • Gert G. Van den Eynden
    • 1
  • Stephen B. Fox
    • 2
  • Fabrizio Bianchi
    • 2
  • Adrian L. Harris
    • 3
  • Peter van Dam
    • 1
  • Eric A. Van Marck
    • 1
  • Peter B. Vermeulen
    • 1
  • Luc Y. Dirix
    • 1
    Email author
  1. 1.Translational Cancer Research Group (Lab Pathology)University of Antwerp/University Hospital Antwerp, Edegem and General HospitalSint-AugustinusBelgium
  2. 2.Nuffield Department of Clinical Laboratory SciencesJohn Radcliffe Hospital, University of OxfordUK
  3. 3.Cancer Research UK Growth Factor GroupWeatherall Institute of Molecular Medicine, John Radcliffe HospitalOxfordUK

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