Clinical significance of cytokeratin 20-positive circulating tumor cells detected by a refined immunomagnetic enrichment assay in colorectal cancer patients.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Detection of CK20 pCTCs using the new protocol could generate clinically important information for colorectal cancer patients.
Wong
Sze Chuen Cesar
SC
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. cesar01@netvigator.com
Chan
Charles Ming Lok
CM
Ma
Brigette Buig Yue
BB
Hui
Edwin Pun
EP
Ng
Simon Siu Man
SS
Lai
Paul Bo San
PB
Cheung
Moon Tong
MT
Lo
Elena Siu Fong
ES
Chan
Amanda Kit Ching
AK
Lam
Money Yan Yee
MY
Au
Thomas Chi Chuen
TC
Chan
Anthony Tak Cheung
AT
D000236:Adenoma / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D045744:Cell Line, Tumor; D002886:Chromosomes, Human, Pair 17; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods*; D053554:Keratin-20 / Q000097:blood*; D009360:Neoplastic Cells, Circulating / Q000737:chemistry*; D011379:Prognosis
D014408:Biomarkers, Tumor; D053554:Keratin-20