Affiliations: Breakthrough Research Unit and Division of Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK | School of Biology, University of St Andrews, St Andrews, UK | Definiens AG, Munich, Germany | Faculty of Medicine, Section of Dermatology, Division of Cancer Sciences, University of Glasgow, Glasgow, UK
Note: [] Corresponding author: Elad Katz, Breakthrough Research Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Tel.: +44 131 537 3154. E-mail: elad.katz@ed.ac.uk These authors contributed equally.
Note: [] These authors contributed equally.
Abstract: Tumour cells employ a variety of mechanisms to invade their environment and to form metastases. An important property is the ability of tumour cells to transition between individual cell invasive mode and collective mode. The switch from collective to individual cell invasion in the breast was shown recently to determine site of subsequent metastasis. Previous studies have suggested a range of invasion modes from single cells to large clusters. Here, we use a novel image analysis method to quantify and categorise invasion. We have developed a process using automated imaging for data collection, unsupervised morphological examination of breast cancer invasion using cognition network technology (CNT) to determine how many patterns of invasion can be reliably discriminated. We used Bayesian network analysis to probabilistically connect morphological variables and therefore determine that two categories of invasion are clearly distinct from one another. The Bayesian network separated individual and collective invading cell groups based on the morphological measurements, with the level of cell-cell contact the most discriminating morphological feature. Smaller invading groups were typified by smoother cellular surfaces than those invading collectively in larger groups. Interestingly, elongation was evident in all invading cell groups and was not a specific feature of single cell invasion as a surrogate of epithelial-mesenchymal transition. In conclusion, the combination of cognition network technology and Bayesian network analysis provides an insight into morphological variables associated with transition of cancer cells between invasion modes. We show that only two morphologically distinct modes of invasion exist.
Keywords: Invasion, imaging, breast cancer, Bayesian networks, EMT
