Circulating tumor cell enumeration for improved screening and disease detection of patients with colorectal cancer

The immunochemical fecal occult blood test (iFOBT) for colorectal cancer (CRC) screening and the serum carcinoembryonic antigen (CEA) assay for disease detection of CRC is associated with a high false-positive rate and a low detection sensitivity, respectively. There is an unmet need to define additional modalities to complement these assays. Different subsets of circulating tumor cells (CTCs) are present in the peripheral blood of cancer patients. Whether or not CTCs testing supplements these clinical assays and is valuable for patients with CRC was investigated.

CTCs were enriched from pre-operative patients with CRC (n = 109) and the non-cancerous controls (n = 65). CTCs expressing either epithelial cell adhesion molecule (EpCAM) or podoplanin (PDPN, the marker associated with poor cancer prognosis) were defined by immunofluorescence staining and were analyzed alone or in combination with iFOBT or serum CEA.

Patients with early or advanced stage of CRC can be clearly identified and differentiated from the non-cancerous controls (p < 0.001) by EpCAM⁺-CTC or PDPN⁺-CTC count. The sensitivity and specificity of EpCAM⁺-CTCs was 85.3% and 78.5%, respectively, when the cutoff value was 23 EpCAM⁺-CTCs/mL of blood; and the sensitivity and specificity of PDPN⁺-CTCs was 78.0% and 75.4%, respectively, when the cutoff value was 7 PDPN⁺-CTCs/mL of blood. Combined analysis of iFOBT with the EpCAM⁺-CTC and PDPN⁺-CTC count reduced the false-positive rate of iFOBT from 56.3% to 18.8% and 23.4%, respectively. Combined analysis of serum CEA with the EpCAM⁺-CTC and PDPN⁺-CTC count increased the disease detection rate from 30.3% to 89.9% and 86.2%, respectively.

CTC testing could supplement iFOBT to improve CRC screening and supplement serum CEA assay for better disease detection of patients with CRC.