A stromal gene signature associated with inflammatory breast cancer

Authors

  • Brenda J. Boersma,

    1. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Mark Reimers,

    1. Genomics and Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Ming Yi,

    1. Advanced Biomedical Computing Center, NCI-Frederick/SAIC-Frederick Inc., Frederick, MD
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  • Joseph A. Ludwig,

    1. Genomics and Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
    2. Department of Sarcoma Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX
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  • Brian T. Luke,

    1. Advanced Biomedical Computing Center, NCI-Frederick/SAIC-Frederick Inc., Frederick, MD
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  • Robert M. Stephens,

    1. Advanced Biomedical Computing Center, NCI-Frederick/SAIC-Frederick Inc., Frederick, MD
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  • Harry G. Yfantis,

    1. Pathology and Laboratory Medicine, Baltimore Veterans Affairs Medical Center, Baltimore, MD
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  • Dong H. Lee,

    1. Pathology and Laboratory Medicine, Baltimore Veterans Affairs Medical Center, Baltimore, MD
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  • John N. Weinstein,

    1. Genomics and Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Stefan Ambs

    Corresponding author
    1. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
    • Laboratory of Human Carcinogenesis, National Cancer Institute, Bldg.37/Room 3050B, Bethesda, MD 20892-4258, USA

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Abstract

The factors that determine whether a breast carcinoma will develop into inflammatory breast cancer (IBC) remain poorly understood. Recent evidence indicates that the tumor stroma influences cancer phenotypes. We tested the hypotheses that the gene expression signature of the tumor stroma is a distinctive feature of IBC. We used laser capture microdissection to obtain enriched populations of tumor epithelial cells and adjacent stromal cells from 15 patients with IBC and 35 patients with invasive, noninflammatory breast cancer (non-IBC). Their mRNA expression profiles were assessed using Affymetrix GeneChips™. In addition, a previously established classifier for IBC was evaluated for the resulting data sets. The gene expression profile of the tumor stroma distinguished IBC from non-IBC, and a previously established IBC prediction signature performed better in classifying IBC using the gene expression profile of the tumor stroma than it did using the profile of the tumor epithelium. In a pathway analysis, the genes differentially expressed between IBC and non-IBC tumors clustered in distinct pathways. We identified multiple pathways related to the endoplasmic stress response that could be functionally significant in IBC. Our findings suggest that the gene expression in the tumor stroma may play a role in determining the IBC phenotype. © 2007 Wiley-Liss, Inc.

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