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

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 and Agnieszka K Witkiewicz
Breast cancer research and treatment, v 133(3), pp 1009-1024
Jun 2012
DOI: https://doi.org/10.1007/s10549-011-1894-3
PMID: 22134623
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Breast Neoplasms - genetics Breast Neoplasms - mortality Breast Neoplasms - pathology Carcinoma, Ductal - genetics Carcinoma, Ductal - mortality Carcinoma, Ductal - pathology Carcinoma, Intraductal, Noninfiltrating - genetics Carcinoma, Intraductal, Noninfiltrating - mortality Carcinoma, Intraductal, Noninfiltrating - pathology Cluster Analysis Disease Progression Epithelial-Mesenchymal Transition - genetics Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Receptors, Estrogen - deficiency Reproducibility of Results Stromal Cells - metabolism Stromal Cells - pathology Survival Analysis
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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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#5 Gender Equality
#3 Good Health and Well-Being

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Web of Science research areas
Oncology
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