期刊
CLINICAL & EXPERIMENTAL METASTASIS
卷 34, 期 6-7, 页码 421-429出版社
SPRINGER
DOI: 10.1007/s10585-017-9858-6
关键词
Breast cancer; Collective invasion; Adipose tissue; Epithelial-to-mesenchymal transition; Cell-cell junctions; E-cadherin; CD44; Distant metastasis
类别
资金
- Graduate School for Life Sciences, University of Wurzburg
- NWO [918.11.626-Vici]
- Cancer Genomics Network
- European Research Council [617430-DEEPINSIGHT]
Breast cancer undergoes collective tissue invasion and, in experimental models, can collectively metastasize. The prevalence of collective invasion and its contribution to distant metastasis in clinical disease, however, remains poorly defined. We here scored the adipose tissue invasion of primary invasive ductal carcinoma (IDC), expressing E-cadherin, and E-cadherin negative invasive lobular carcinoma (ILC) and identified predominantly collective invasion patterns (86/86 samples) in both carcinoma types. Whereas collective invasion in IDC lesions retained adherens junctions, multicellular clusters and Indian files in ILC, despite the absence of adherens junctions (AJ) proteins E-cadherin and beta-catenin, retained CD44 at cell-cell contacts. By histomorphological scoring and semi-automated image analysis, we show that the extent of collective invasion into the adipose tissue correlated with decreased distant metastasis-free survival (5-year follow-up; hazard ratio: 2.32 and 2.29, respectively). Thus, collective invasion represents the predominant invasion mode in breast cancer, develops distinct junctional subtypes in IDC and ILC, and associates with distant metastasis, suggesting a critical role in systemic dissemination.
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