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.
