Circulating epithelial cells in patients with benign colon diseases.
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.
Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Klaus
K
Pantel
Eric
E
Denève
David
D
Nocca
Amandine
A
Coffy
Jean-Pierre
JP
Vendrell
Thierry
T
Maudelonde
Sabine
S
Riethdorf
Catherine
C
Alix-Panabières
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood / Q000276:immunology; D002452:Cell Count; D003108:Colonic Diseases / Q000097:blood / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000473:pathology*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000097:blood / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000097:blood; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D013194:Staining and Labeling; D055815:Young Adult
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human