New Approaches for Early Detection of Breast Tumor Invasion or Progression

Abstract

Abstract : To assess interactions between epithelial (EP) and myoepithelial (ME) cells in association with breast tumor progression and invasion, a double immunostaining technique with antibodies to smooth muscle actin (SMA) and estrogen receptor (ER) was used to elucidate the ME and EP cells in breast tissues harboring ductal carcinoma in situ (DCIS). Single or clusters of EP cells with a marked diminution or a total loss of the ER expression were found immediately overlying focally disrupted ME cell layers. These tumor cells showed several unique features, including a significantly higher rate of proliferation, genetic instability, and expression of tumor invasion-related genes. This was in sharp contrast to the adjacent dominant population of ER (+) cells within the same duct that showed no associated ME cell layer disruptions. This study attempted to confirm the authors' previous findings on a larger number of cases, and to compare the immunohistochemical and molecular biological profiles of the ER (-) cells overlying disrupted ME cell layers with those of adjacent ER (+) cells and surrounding stromal (ST) cells. Since ME cell layers are physical barriers protecting the microenvironment and integrity of EP cells, and the disruption of ME cell layers is an absolute pre-requisite for breast tumor invasion, the outcomes of this project could have significant value in early detection of breast tumor invasion and/or progression. The authors suggest that focal ME layer disruptions might represent an early sign of tumor invasion, and that cells overlying focal ME layer disruptions might represent precursors of invasive lesions. They have further proposed that breast tumor invasion is triggered by a localized degeneration of injured or aged ME cells and resultant immunoreactions, which stimulate tumor stem cells to proliferate and invade.