Towards a multiscale model of colorectal cancer

Figure 5 The stages of tumour development. Colorectal cancers develop through a variety of stages. Disruption of Wnt signalling (usually through APC mutation) will cause adenoma formation. This is manifest as dysplasia of the epithelial cells (characterised by enlargement of the epithelial nuclei, loss of mucin and deeply staining nuclei). Adenomas can grow by crypt branching and colonisation of other crypts but, importantly, remain bounded by the basement membrane. The branching of the crypts causes adenomas to develop a very complex architecture and, as more mutations accrue, the architecture becomes more complex and the cells become more severely dysplastic. Eventually the tumour cells will break through the basement membrane and invade into the stroma and this represents the transition from and adenoma into a carcinoma. Once within the stroma, the tumour cells can grow, infiltrate more deeply into the bowel wall and also can invade into lymphatic and vascular structures to allow metastasis to distant sites, such as lymph nodes. It is noteworthy that metastatic deposits also contain stroma showing the importance of the relationship between the tumour epithelium and the tumour stroma.