Focal myoepithelial cell layer disruptions and basement membrane disappearance are correlated events: Implications for breast tumor invasion

Abstract

Our previous studies showed that a subset of ductal carcinoma in situ (DCIS) showed focal disruptions in their surrounding myoepithelial (ME) cell layers, and that tumor cells overlying these disruptions had a significantly higher rate of proliferation, genetic instability, and expression of tumor invasion-related genes than adjacent cells within the same duct. Since the ME cell layer and basement membrane (BM) are intercalated structures, our current study intended to assess if these two structures would show correlated alterations. Consecutive sections from pure DCIS and DCIS with co-existing invasive ductal carcinoma (IDC) were double immunostained for collagen IV and smooth muscle actin. The frequency and locations of focal ME cell layer and BM disruptions were compared. In ducts with a non-disrupted ME cell layer, the BM layer formed a densely packed band with uniform thickness that completely surrounded the ME cell layer. In ducts with a fragmented ME cell layer, the associated BM layer was generally thin, discontinues, or diffuse. All focal ME cell layer disruptions encountered were companied by the focal disappearance of the BM on the same site. Of these disruptions, over 80% were seen in DCIS and over 15% were seen in normal and hyperplastic ducts. The frequency and size of these disruptions were significantly higher and larger in tumors with coexisting DCIS and IDC than in pure DCIS. These findings suggest that the physical integrity of the ME cell layer may be necessary for maintaining the normal structure and functions of the BM.