Article

Wong SC, Chan CM, Ma BB, Hui EP, Ng SS, Lai PB, Cheung MT, Lo ES, Chan AK, Lam MY, Au TC, Chan ATClinical significance of cytokeratin 20-positive circulating tumor cells detected by a refined immunomagnetic enrichment assay in colorectal cancer patients. Clin Cancer Res 15: 1005-1012

State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute and Prince of Wales Hospital, People's Republic of China.
Clinical Cancer Research (Impact Factor: 8.72). 03/2009; 15(3):1005-12. DOI: 10.1158/1078-0432.CCR-08-1515
Source: PubMed

ABSTRACT

Current immunomagnetic enrichment method can only detect general epithelial antigens of circulating tumor cells (CTC). Further characterization of the CTCs to provide specific information on the tumor type is not possible. We attempted to overcome this drawback by developing the methodology for using a gastrointestinal-specific anti-cytokeratin (CK) 20 antibody to detect CTCs in colorectal cancer patients' blood.
The protocol was validated using a colorectal cancer SW480 cell line. The clinical significance of findings in colorectal cancer was investigated by detecting CK20-positive CTCs (pCTC) in patients with colorectal cancer, other common cancers, colorectal adenoma, benign colorectal diseases, and normal subjects. Moreover, the malignant nature of CK20 pCTCs was examined by comparing chromosome 17 aberration patterns with those from the corresponding primary tumors.
The assay successfully showed CK20-positive SW480 cells. When applied in patient samples, the detection rates were 62% (132 colorectal cancer patients; median number = 11 CTCs), 0% (120 patients with other common cancers), 6% (50 colorectal adenoma patients), 0% (120 patients with benign colorectal diseases), and 0% (40 normal subjects). Furthermore, statistical analysis showed that CK20 pCTC numbers were associated with tumor-node-metastasis stage and lymph node status. Using the median CK20 pCTC numbers as the cutoff points, stratified groups of colorectal cancer patients had significant differences in their recurrence, metastasis, and survival. Finally, chromosome 17 aneusomy in 90% of colorectal cancer patients with CK20 pCTCs matched with those from the primary tumors.
Detection of CK20 pCTCs using the new protocol could generate clinically important information for colorectal cancer patients.

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    • "Moreover, metastasis and recurrence were shown to occur at an earlier time in a patient who showed expression of circulating tumor cells [3, 8], and their survival rate was reported to be lower as well [3, 13]. According to the study of Wong et al. [14], among the patients suffering from colorectal cancer with the presence of circulating tumor cells, 88% showed decreased levels of such cells after surgery. Similar results were observed in this study. "
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    • "17-1440-02; GE Healthcare, Uppsala, Sweden), according to the manufacturer's instructions. The CTCs were isolated from the mononuclear cells using the refined protocol as shown in our recent study (Wong et al, 2009) and CDX2 ICC staining was performed for each patient sample. The criteria used to identify CDX2 pCTCs in a blood sample were as follows: (1) positive CDX2 staining, (2) the cell should have a round-to-oval morphology and (3) the cell size should be at least double that of a lymphocyte. "
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