Prognostic relevance of minimal residual disease in colorectal cancer

Figure 1 Model of the metastatic cascade in colorectal cancer. Cancer cells (red cells in Figure 1) are released from the primary tumor and enter the circulation and/or the lymphatic system (lymphatic vessels and lymph nodes) by various mechanisms, such as epithelial mesenchymal transition. The circulating tumor cells in the circulation are called circulating tumor cells (CTC) and may form distant metastases, for colorectal cancer (CRC) commonly in the liver and lung. However, more than 90% of the CTC in the vascular system will undergo cell death and will not have the malignant traits necessary to form distant metastases. Disseminated tumor cells (DTC) in the lymph nodes can either form micrometastases or remain in the lymph nodes as isolated tumor cells which are not detected by conventional HE staining. Cross talk between the vascular and lymphatic system likely exists and it is hypothesized that disseminated tumor cells in the lymphatic system may also form distant metastases. It is also assumed that metastases themselves have the capacity to release tumor cells back into the systemic or vascular circulation. Cross talk also exists with DTC (not shown in the figure) in the bone marrow, where cells enter from the blood-stream and remain in a silent state for several years before they may reenter the circulation to form distant metastases. Dotted lines indicate hypothesized pathways and straight lines show established and accepted mechanisms of tumor cell dissemination.