Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress

Abstract

Circulating tumor cells (CTC) may be defined as tumor-or metastasis-derived cells that are present in the bloodstream. The CTC pool in colorectal cancer (CRC) patients may include not only epithelial tumor cells, but also tumor cells undergoing epithelial-mesenchymal transition (EMT) and tumor stem cells. A significant number of patients diagnosed with early stage CRC subsequently relapse with recurrent or metastatic disease despite undergoing "curative" resection of their primary tumor. This suggests that an occult metastatic disease process was already underway, with viable tumor cells being shed from the primary tumor site, at least some of which have proliferative and metastatic potential and the ability to survive in the bloodstream. Such tumor cells are considered to be responsible for disease relapse in these patients. Their detection in peripheral blood at the time of diagnosis or after resection of the primary tumor may identify those early-stage patients who are at risk of developing recurrent or metastatic disease and who would benefit from adjuvant therapy. CTC may also be a useful adjunct to radiological assessment of tumor response to therapy. Over the last 20 years many approaches have been developed for the isolation and characterization of CTC. However, none of these methods can be considered the gold standard for detection of the entire pool of CTC. Recently our group has developed novel unbiased inertial microfluidics to enrich for CTC, followed by identification of CTC by imaging flow cytometry. Here, we provide a review of progress on CTC detection and clinical significance over the last 20 years.

Circulating tumor microemboli (CTM) and vimentin+ circulating tumor cells (CTCs) detected by a size-based platform predict worse prognosis in advanced colorectal cancer patients during chemotherapy

“…Moreover, CTC count was increasing with decreasing tumor de-differentiation, increasing lymphatic invasion, TNM stage, and serum CEA level. Therefore, although the decisions on stage of disease still did not include the results of CTC assessment, the presence of CTCs might be an adjunct to staging [32], and it could be expected that CTC detection predicted the properties and processes of the disease (e.g. lymphatic invasion, TNM stage, and serum CEA level).…”

FAM172A expression in circulating tumor cells for prediction of high-risk subgroups of colorectal cancer

“…Besides, this approach would miss CTCs that have low levels of EpCAM expression and fail to detect the most aggressive CTC subpopulation, which may have undergone EMT 29. For example, the rarity of CTCs in early CRC was illustrated in a study of 20 consecutive patients undergoing curative resection for stages I–III CRC 30. The detection rate using CellSearch system was 5% in the preoperative samples, using a cutoff of 2 CTCs/7.5 mL.…”

Clinical and biological significance of circulating tumor cells in cancer

“…Despite some shortcomings, CTCs detected by the CellSearch system are thought to be useful biomarkers for diagnosis (Beije et al., 2015). However, CTCs have not yet been fully accepted in clinical practice for guiding treatment decisions in individual cancer patients because of problems associated with sensitivity and specificity (Hardingham et al., 2015). As discussed below, further studies are needed to overcome these limitations.…”