Comparisons of Gene Expression Patterns in Progressive Breast Carcinoma and the Adjacent Stromal Microenvironment

Abstract

Human breast ductal carcinoma in situ (DCIS) is categorized as Stage 0 because it is noninvasive and limited to the duct lining. However, women diagnosed with DCIS have a 30-40% chance of developing invasive breast cancer (IBC) if it is left untreated. The breast tissue microenvironment of the surrounding stroma plays an important role in the malignant invasion and migration of tumor cells across the basement membrane, which separates the epithelial cells from the stroma in the normal breast. Far from being passive, the stroma plays an active role in invasiveness and perhaps throughout the entire progression of malignancy. Complex signaling networks, both intracellular and extracellular, are activated along with dramatic extracellular matrix (ECM) remodeling and growth factor release, which in turn leads to significant changes in cellular gene expression profiles. This study examines those gene expression profiles across the full range of breast cancer progression from normal to hyperplasia through DCIS and IBC, looking specifically at changes in gene expression between the cancerous epithelial tissue and the surrounding stroma, using the recent advancement of laser capture microdissection to obtain highly purified, cell type specific samples.