Capture of Viable Circulating Tumor Cells in the Liver of Colorectal Cancer Patients

Author:

Denève Eric1,Riethdorf Sabine2,Ramos Jeanne3,Nocca David1,Coffy Amandine4,Daurès Jean-Pierre4,Maudelonde Thierry5,Fabre Jean-Michel1,Pantel Klaus2,Alix-Panabières Catherine456

Affiliation:

1. Department of Digestive Surgery and

2. Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

3. Department of Pathology, University Medical Centre, Gui de Chauliac Hospital, Montpellier, France

4. University Institute of Clinical Research UM1, EA2415, Epidemiology, Biostatistics & Public Health, Montpellier, France

5. Cell and Tissue Biopathology of Tumors Department, University Medical Centre, Saint Eloi Hospital, Montpellier, France

6. Institute of Research in Biotherapy, Laboratory of Rare Human Circulating Cells, University Medical Centre, Saint-Eloi Hospital, Montpellier, France

Abstract

BACKGROUND The incidence and number of circulating tumor cells (CTCs) in the peripheral blood of colorectal cancer patients are lower than in other cancer types, which may point to a particular biology of colorectal cancer affecting CTC detection. METHODS We detected CTCs in the peripheral and mesenteric blood of colorectal cancer patients by use of 2 independent technologies on the basis of different biological properties of colon cancer cells. Seventy-five patients diagnosed with localized (M0, n = 60) and metastatic (M1, n = 15) colorectal cancer were included. Peripheral and mesenteric blood samples were collected before tumor resection. We performed CTC enumeration with an EpCAM-independent enrichment method followed by the Epispot assay that detected only viable CK19-releasing CTCs. In parallel, we used the FDA-cleared EpCAM-dependent CellSearch® as the reference method. RESULTS The enumeration of CK19-releasing cells by the CK19-Epispot assay revealed viable CTCs in 27 of 41 (65.9%) and 41 of 74 (55.4%) (P = 0.04) patients in mesenteric and peripheral blood, respectively, whereas CellSearch detected CTCs in 19 of 34 (55.9%) and 20 of 69 (29.0%) (P = 0.0046) patients. In mesenteric blood, medians of 4 (range 0–247) and 2.7 CTCs (range 0–286) were found with Epispot and CellSearch (P = 0.2), respectively, whereas in peripheral blood, Epispot and CellSearch detected a median of 1.2 (range 0–92) and 0 CTCs (range 0–147) (P = 0.002). CONCLUSIONS A considerable portion of viable CTCs detectable by the Epispot assay are trapped in the liver as the first filter organ in CRC patients.

Funder

European Commission

European Research Council Investigator

Publisher

Oxford University Press (OUP)

Subject

Biochemistry, medical,Clinical Biochemistry

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