avb6 Expression in Myoepithelial Cells: A Novel Marker for Predicting DCIS Progression with Therapeutic Potential

The tumor microenvironment dynamically regulates the progression of cancer. In the breast, a unique component of the microenvironment is the myoepithelial cell. Normal myoepithelial cells act as "natural tumor suppressors"; however, more recent evidence suggests that these cells develop phenotypic changes, which may contribute to loss of tumor suppressor activity. We have shown that myoepithelial cells in a subset of preinvasive ductal carcinoma in situ (DCIS) upregulate expression of the integrin avb6, switching on tumor promoter activity through activation of TGFb and MMP9. This makes the tumor microenvironment more permissive to invasion, seen both in vitro and in vivo. In human tissue samples, increased myoepithelial avb6 expression correlated with increased risk of disease progression and recurrence. Current estimates suggest that as many as 50% of DCIS cases will never progress in the patient's lifetime, but there are no markers to predict the outcome of individual cases. The identification of avb6 in a subset of DCIS presents a unique way to stratify patients with DCIS into those who may or may not progress to more serious disease. As avb6 is not expressed on most normal adult tissues, this finding may also provide novel targets for therapy in this highrisk group. Cancer Res; 74(21); 5942–7. 2014 AACR.