BACKGROUND: Detection of circulating tumor cells (CTCs) in the peripheral blood is a rapidly developing research field with clear clinical implications for the staging and monitoring of cancer patients. Current CTC assays, including the US Food and Drug Administration-cleared CellSearch® system, typically use markers [e.g., cytokeratins (CKs), the transmembrane protein EpCAM (epithelial cell adhesion molecule)] that are expressed on normal and malignant epithelial cells but not on the surrounding normal leukocytes. METHODS: We enrolled 53 patients with benign colon diseases (e.g., diverticulosis, benign polyps, Crohn disease, ulcerative rectocolitis, colonic endometriosis) and analyzed their peripheral blood with 2 previously validated CTC assays: the epithelial immunospot (EPISPOT) assay and the CellSearch system. The EPISPOT assay detects only viable, CK19-releasing CTCs that were enriched by depletion of CD45(+) leukocytes, whereas the CellSearch system detects CK-positive CTCs after positive EpCAM-based immunomagnetic enrichment. RESULTS: In patients with benign colon diseases, positive events that met the criteria for "tumor cells" were detected with both the CellSearch system (11.3%) and the CK19-EPISPOT assay (18.9%), whereas no positive events were detected in samples from healthy volunteers. Positive events were detected most frequently in patients with diverticulosis and Crohn disease. All positive events lacked expression of CD45, a common leukocyte antigen. CONCLUSIONS: These results indicate that patients with benign inflammatory colon diseases in particular can harbor viable circulating epithelial cells that are detectable with current CTC assays. This finding points to the need for further molecular characterization of circulating epithelial cells and has important implications for the use of CTC testing.
BACKGROUND: Detection of circulating tumor cells (CTCs) in the peripheral blood is a rapidly developing research field with clear clinical implications for the staging and monitoring of cancerpatients. Current CTC assays, including the US Food and Drug Administration-cleared CellSearch® system, typically use markers [e.g., cytokeratins (CKs), the transmembrane protein EpCAM (epithelial cell adhesion molecule)] that are expressed on normal and malignant epithelial cells but not on the surrounding normal leukocytes. METHODS: We enrolled 53 patients with benign colon diseases (e.g., diverticulosis, benign polyps, Crohn disease, ulcerative rectocolitis, colonic endometriosis) and analyzed their peripheral blood with 2 previously validated CTC assays: the epithelial immunospot (EPISPOT) assay and the CellSearch system. The EPISPOT assay detects only viable, CK19-releasing CTCs that were enriched by depletion of CD45(+) leukocytes, whereas the CellSearch system detects CK-positive CTCs after positive EpCAM-based immunomagnetic enrichment. RESULTS: In patients with benign colon diseases, positive events that met the criteria for "tumor cells" were detected with both the CellSearch system (11.3%) and the CK19-EPISPOT assay (18.9%), whereas no positive events were detected in samples from healthy volunteers. Positive events were detected most frequently in patients with diverticulosis and Crohn disease. All positive events lacked expression of CD45, a common leukocyte antigen. CONCLUSIONS: These results indicate that patients with benign inflammatory colon diseases in particular can harbor viable circulating epithelial cells that are detectable with current CTC assays. This finding points to the need for further molecular characterization of circulating epithelial cells and has important implications for the use of CTC testing.
Authors: Anders Carlsson; Viswam S Nair; Madelyn S Luttgen; Khun Visith Keu; George Horng; Minal Vasanawala; Anand Kolatkar; Mehran Jamali; Andrei H Iagaru; Ware Kuschner; Billy W Loo; Joseph B Shrager; Kelly Bethel; Carl K Hoh; Lyudmila Bazhenova; Jorge Nieva; Peter Kuhn; Sanjiv S Gambhir Journal: J Thorac Oncol Date: 2014-08 Impact factor: 15.609
Authors: Colin M Court; Shuang Hou; Paul Winograd; Nicholas H Segel; Qingyu Wilda Li; Yazhen Zhu; Saeed Sadeghi; Richard S Finn; Ekambaram Ganapathy; Min Song; Samuel W French; Bita V Naini; Shonan Sho; Fady M Kaldas; Ronald W Busuttil; James S Tomlinson; Hsian-Rong Tseng; Vatche G Agopian Journal: Liver Transpl Date: 2018-07 Impact factor: 5.799
Authors: Edwin E Reyes; Marc Gillard; Ryan Duggan; Kristen Wroblewski; Steven Kregel; Masis Isikbay; Jacob Kach; Hannah Brechka; David J Vander Weele; Russell Z Szmulewitz; Donald J Vander Griend Journal: J Transl Sci Date: 2015-07-30