Breast Cancer Research and Treatment

, Volume 138, Issue 3, pp 761–772

Genomic and expression analysis of microdissected inflammatory breast cancer

  • Wendy A. Woodward
  • Savitri Krishnamurthy
  • Hideko Yamauchi
  • Randa El-Zein
  • Dai Ogura
  • Eri Kitadai
  • Shin-ichiro Niwa
  • Massimo Cristofanilli
  • Peter Vermeulen
  • Luc Dirix
  • Patrice Viens
  • Steve van Laere
  • François Bertucci
  • James M. Reuben
  • Naoto T. Ueno
Preclinical study

Abstract

Inflammatory breast cancer (IBC) is a unique clinical entity characterized by rapid onset of erythema and swelling of the breast often without an obvious breast mass. Many studies have examined and compared gene expression between IBC and non-IBC (nIBC), repeatedly finding clusters associated with receptor subtype, but no consistent gene signature associated with IBC has been validated. Here we compared microdissected IBC tumor cells to microdissected nIBC tumor cells matched based on estrogen and HER-2/neu receptor status. Gene expression analysis and comparative genomic hybridization were performed. An IBC gene set and genomic set were identified using a training set and validated on the remaining data. The IBC gene set was further tested using data from IBC consortium samples and publicly available data. Receptor driven clusters were identified in IBC; however, no IBC-specific gene signature was identified. Fifteen genes were correlated between increased genomic copy number and gene overexpression data. An expression-guided gene set upregulated in the IBC training set clustered the validation set into two clusters independent of receptor subtype but segregated only 75 % of samples in each group into IBC or nIBC. In a larger consortium cohort and in published data, the gene set failed to optimally enrich for IBC samples. However, this gene set had a high negative predictive value for excluding the diagnosis of IBC in publicly available data (100 %). An IBC enriched genomic data set accurately identified 10/16 cases in the validation data set. Even with microdissection, no IBC-specific gene signature distinguishes IBC from nIBC. Using microdissected data, a validated gene set was identified that is associated with IBC tumor cells. Inflammatory breast cancer comparative genomic hybridization data are presented, but a validated genomic data set that identifies IBC is not demonstrated.

Keywords

Inflammatory breast cancer  CGH  Array  Gene signature 

Supplementary material

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Supplementary material 1 (PPT 219 kb)
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Supplementary material 2 (PPT 271 kb)
10549_2013_2501_MOESM3_ESM.xls (31 kb)
Supplementary material 3 (XLS 31 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Wendy A. Woodward
    • 1
    • 8
  • Savitri Krishnamurthy
    • 2
    • 8
  • Hideko Yamauchi
    • 3
  • Randa El-Zein
    • 4
    • 8
  • Dai Ogura
    • 5
  • Eri Kitadai
    • 3
  • Shin-ichiro Niwa
    • 5
  • Massimo Cristofanilli
    • 7
    • 8
  • Peter Vermeulen
    • 10
  • Luc Dirix
    • 10
  • Patrice Viens
    • 9
  • Steve van Laere
    • 10
    • 11
  • François Bertucci
    • 9
  • James M. Reuben
    • 6
    • 8
  • Naoto T. Ueno
    • 7
    • 8
  1. 1.Departments of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Departments of PathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Breast SurgerySt. Luke’s International HospitalTokyoJapan
  4. 4.Departments of EpidemiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Link Genomics Inc.TokyoJapan
  6. 6.Departments of HematopathologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Departments of Breast Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  8. 8.Morgan Welch Inflammatory Breast Cancer Research Program and ClinicThe University of Texas MD Anderson Cancer CenterHoustonUSA
  9. 9.The Department of Medical OncologyInstitut Paoli-CalmettesMarseilleFrance
  10. 10.Translational Cancer Research UnitSint-Augustinus HospitalAntwerpBelgium
  11. 11.Department of OncologyKU LeuvenLeuvenBelgium

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