Clinical Significance of Cytokeratin 20-Positive Circulating Tumor Cells Detected by a Refined Immunomagnetic Enrichment Assay in Colorectal Cancer Patients

Abstract

Purpose: 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. Experimental Design: 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.

Immunohistochemical Expression of Cytokeratin 20in Colorectal Tumors Among Sudanese Patients.

“…The detected expression in the current study was lower than most of the reported data (9,14) .For instance reported higher expression values of CK20 in colorectal cancer (80%) (9) . Moreover, other studies showed higher frequencies of CK20 in colorectal adenocarcinomas reaching 81% and 84% (17,18) .It's also important to highlight the significance of the reported negative immunohistochemical expression of CK20 in this study (42%) which was associated with higher microsatellite instability in previous studies and thus bad prognosis (19) .…”

Jagged 2 silencing inhibits motility and invasiveness of colorectal cancer cell lines

“…These findings provide support to the hypothesis that JAG2 functions to promote metastasis in multiple cancer types. It would be of interest to investigate whether JAG2 is expressed in circulating tumor cells of CRC patients, as these cells have been demonstrated to be associated with tumor-node-metastasis stage and lymph node status (21,22). In addition, the clinical value of JAG2 as a novel biomarker in CRC warrants further study (23).…”

The clinical significance of circulating tumor cells in non-metastatic colorectal cancer – A review

“…Following inclusion criteria for studies were set: (1) patients diagnosed with non-metastatic colorectal cancer (TNM-stage I-III), (2) CTC detected in peripheral blood samples, (3) pre-and/or postoperative blood samples and (4) samples size of ≥99 patients. Nine studies qualified for further analyses (Table 1) [ [18][19][20][21][22][23][24][25][26].…”