title: 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.
authors.affiliation: Molecular Oncology Group, Haematology-Oncology Department, Basil Hetzel Institute, The Queen Elizabeth Hospital, Woodville, South Australia.|School of Medicine, University of Adelaide, South Australia.|Centre for Personalized Medicine, University of Adelaide, South Australia.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Hardingham
authors.affiliation: Department of Surgery, The Queen Elizabeth Hospital, Woodville, South Australia.
authors.forename: Phulwinder
authors.initials: P
authors.lastname: Grover
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes, South Australia.
authors.forename: Marnie
authors.initials: M
authors.lastname: Winter
authors.affiliation: Department of Surgery, The Queen Elizabeth Hospital, Woodville, South Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hewett
authors.affiliation: School of Medicine, University of Adelaide, South Australia.|Medical Oncology, The Queen Elizabeth Hospital, Woodville, South Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Price
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes, South Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Thierry
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000266:history* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D044085:Microfluidics / Q000295:instrumentation; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012008:Recurrence
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D016179:Granulocyte Colony-Stimulating Factor; D043562:Receptors, G-Protein-Coupled; C065501:ASCL2 protein, human; C116884:LGR5 protein, human; C454127:OLFM4 protein, human