Breast Cancer Research and Treatment

, Volume 138, Issue 3, pp 761–772

Genomic and expression analysis of microdissected inflammatory breast cancer

Authors

  • Wendy A. Woodward
    • Departments of Radiation OncologyThe University of Texas MD Anderson Cancer Center
    • Morgan Welch Inflammatory Breast Cancer Research Program and ClinicThe University of Texas MD Anderson Cancer Center
  • Savitri Krishnamurthy
    • Departments of PathologyThe University of Texas MD Anderson Cancer Center
    • Morgan Welch Inflammatory Breast Cancer Research Program and ClinicThe University of Texas MD Anderson Cancer Center
  • Hideko Yamauchi
    • Department of Breast SurgerySt. Luke’s International Hospital
  • Randa El-Zein
    • Departments of EpidemiologyThe University of Texas MD Anderson Cancer Center
    • Morgan Welch Inflammatory Breast Cancer Research Program and ClinicThe University of Texas MD Anderson Cancer Center
  • Dai Ogura
    • Link Genomics Inc.
  • Eri Kitadai
    • Department of Breast SurgerySt. Luke’s International Hospital
  • Shin-ichiro Niwa
    • Link Genomics Inc.
  • Massimo Cristofanilli
    • Departments of Breast Medical OncologyThe University of Texas MD Anderson Cancer Center
    • Morgan Welch Inflammatory Breast Cancer Research Program and ClinicThe University of Texas MD Anderson Cancer Center
  • Peter Vermeulen
    • Translational Cancer Research UnitSint-Augustinus Hospital
  • Luc Dirix
    • Translational Cancer Research UnitSint-Augustinus Hospital
  • Patrice Viens
    • The Department of Medical OncologyInstitut Paoli-Calmettes
  • Steve van Laere
    • Translational Cancer Research UnitSint-Augustinus Hospital
    • Department of OncologyKU Leuven
  • François Bertucci
    • The Department of Medical OncologyInstitut Paoli-Calmettes
  • James M. Reuben
    • Departments of HematopathologyThe University of Texas MD Anderson Cancer Center
    • Morgan Welch Inflammatory Breast Cancer Research Program and ClinicThe University of Texas MD Anderson Cancer Center
    • Departments of Breast Medical OncologyThe University of Texas MD Anderson Cancer Center
    • Morgan Welch Inflammatory Breast Cancer Research Program and ClinicThe University of Texas MD Anderson Cancer Center
Preclinical study

DOI: 10.1007/s10549-013-2501-6

Cite this article as:
Woodward, W.A., Krishnamurthy, S., Yamauchi, H. et al. Breast Cancer Res Treat (2013) 138: 761. doi:10.1007/s10549-013-2501-6

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

10549_2013_2501_MOESM1_ESM.ppt (219 kb)
Supplementary material 1 (PPT 219 kb)
10549_2013_2501_MOESM2_ESM.ppt (270 kb)
Supplementary material 2 (PPT 271 kb)
10549_2013_2501_MOESM3_ESM.xls (31 kb)
Supplementary material 3 (XLS 31 kb)

Copyright information

© Springer Science+Business Media New York 2013