Study of matrix metalloproteinases and their tissue inhibitors in ductal in situ carcinomas of the breast

Aims: To analyse the expression of metalloproteinases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ of the breast (DCIS). Methods and results: An immunohistochemical study was performed in 56 patients with pure DCIS, in 39 with DCIS adjacent to invasive carcinoma (IDC) and 63 patients with T1 IDC, using tissue microarrays and specific antibodies against MMPs and TIMPs. Immunohistochemical results were categorized using a specific software program. The data were analysed by unsupervised hierarchical cluster analysis by each cellular type. IDC showed a higher expression rate of MMP‐7 and TIMP‐1 than pure DCIS, as well as a higher expression rate of MMP‐9 and TIMP‐3 than the DCIS component of mixed cases, whereas pure DCIS showed a higher rate of expression of MMP‐9 and ‐11 and TIMP‐3 than in the DCIS component of mixed cases. Pure DCIS with a periductal inflammatory infiltrate showed significantly higher MMP‐2, ‐14 and TIMP‐1. Dendograms identified two cluster groups with distinct MMP/TIMP expression profiles in neoplastic cells and fibroblastic or mononuclear inflammatory cells surrounding the neoplastic ducts of pure DCIS. Conclusions: The results indicate the distinct variability in MMP/TIMP expression by DCIS, which may be of potential biological and clinical interest in breast cancer.