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

Erik S. Knudsen, Adam Ertel, Elai Davicioni, Jessica Kline, Gordon F. Schwartz, Agnieszka K. Witkiewicz

Research output: Contribution to journalArticle

52 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1009-1024
Number of pages16
JournalBreast Cancer Research and Treatment
Volume133
Issue number3
DOIs
StatePublished - Jun 1 2012

Keywords

  • Disease progression
  • Ductal carcinoma in situ
  • EMT
  • Invasive breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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