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Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia

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Abstract

Ductal carcinoma in situ (DCIS) is a precursor lesion that can gives rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue from pure DCIS and pure IBC were employed to define key gene expression profiles in either the epithelial or stromal compartment associated with disease progression. Each tissue had distinct gene expression profiles, and a DCIS/IBC classifier accurately distinguished DCIS versus IBC in multiple independent data sets. However, contrary to other studies that profiled DCIS associated with invasive disease, we found that the most significant alterations in gene expression were observed in the epithelial compartment rather than in the stroma. In particular, genes associated with epithelial-to-mesenchymal transition and myoepithelial cell-specific genes were enriched in invasive cancer relative to pure DCIS. Such alterations in transcript levels were associated with all subtypes of breast cancer, but were particularly indicative of poor outcome in ER-negative breast cancer. Together, these studies indicate that lesion-specific differences in gene expression associated with invasive phenotype are particularly relevant in the progression of DCIS to invasive breast cancer.

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Conflict of interest

Authors Knudsen, Ertel, Kline, Schwartz, and Witkiewicz declare that they have no conflict of interest. Author Dr. Elai Davicioni declares remuneration and stock ownership in GenomeDx Biosciences, Inc.

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Authors and Affiliations

  1. Department of Pathology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Jessica Kline & Agnieszka K. Witkiewicz

  2. Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Erik S. Knudsen, Adam Ertel, Gordon F. Schwartz & Agnieszka K. Witkiewicz

  3. Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Erik S. Knudsen & Adam Ertel

  4. Cancer Genomics Unit, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Adam Ertel

  5. Department of Surgery, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Gordon F. Schwartz

  6. GenomeDx Biosciences Inc., Vancouver, BC, Canada

    Elai Davicioni

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  1. Erik S. Knudsen
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Correspondence to Agnieszka K. Witkiewicz.

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Knudsen, E.S., Ertel, A., Davicioni, E. et al. Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia. Breast Cancer Res Treat 133, 1009–1024 (2012). https://doi.org/10.1007/s10549-011-1894-3

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  • DOI: https://doi.org/10.1007/s10549-011-1894-3

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