CEC testing is a useful tool for analysis of overall survival and remission status of patients with thyroid cancer. Implementation of CEC testing into routine clinical test may be worthy to consider for patient clinical care.

Loco-regional recurrence or distant metastasis usually leads to the death of patients with papillary thyroid carcinoma (PTC). Whether or not circulating epithelial cells (CECs) count is a valuable marker in monitoring the therapeutic outcome of PTC was investigated. Patients with PTC (n=129) were treated in our medical center and were categorized into 4 groups with excellent (n=45), biochemical incomplete (n=15), indeterminate (n=37), and structural incomplete (n=32) responses. CECs were enriched from the peripheral blood by the PowerMag negative selection system. Three subtypes of CECs expressing epithelial cell adhesion molecule (EpCAM), thyroid-stimulating hormone receptor (TSHR, a marker for thyroid cells), and podoplanin (PDPN, a marker related to poor prognosis in patients with PTC) were defined by immunofluorescence staining, respectively. The median number of CECs (cells/mL of blood) expressing EpCAM, TSHR, and PDPN was 23 (interquartile range 10-61), 19 (interquartile range 8-50), and 8 (interquartile range 3-22), respectively, for patients enrolled in this study. The number of EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was statistically different among patients in different treatment response groups without interference from anti-thyroglobulin antibody (P<0.0001). Patients with structural incomplete response had higher counts for all three CECs subtypes when compared to other patients. EpCAM+-CECs was better in distinguishing patients with excellent response from structural incomplete response among the three subtypes of CECs. The sensitivity and specificity of the assay was 84.4% and 95.6%, respectively, when the cut off value was 39 EpCAM+-CECs/mL. CECs testing can supplement the current standard methods for monitoring the therapeutic outcome of PTC.

Patients with thyroid cancer usually have good prognosis. However, 15-20% of patients ultimately develop recurrence and disease-related death. In this study, we investigate whether the number of circulating tumor cells (CTCs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN, a marker related to poor prognosis in patients with thyroid cancer), or thyroid-stimulating hormone receptor (TSHR, a marker for thyroid cells) is a prognostic marker for non-remission and disease-specific mortality (DSM) of patients with thyroid cancer. Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. After enrichment of CTCs by a negative selection PowerMag system, enumeration and subtyping of the CD45-depleted cells were performed by immunofluorescence staining using the antibodies aginst EpCAM, TSHR, and PDPN, respectively. Our data revealed that the number of EpCAM+-CTCs (p &lt; 0.001) and PDPN+-CTCs (p &lt; 0.001), and TSHR+-CTCs (p &lt; 0.001) for patients in the non-remission group (n = 43) was significantly higher when compared to the remission group (n = 85). At the cutoff of 40, 14, and 47 cells/mL for EpCAM+-CTCs, TSHR+-CTCs, and PDPN+-CTCs, the accuracy of the assay was equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the number of EpCAM+-CTCs (p &lt; 0.001), PDPN+-CTCs (p = 0.013), and TSHR+-CTCs (p &lt; 0.001) for patients in the DSM group (n = 17) was significantly higher when compared to the patients who survived (n = 111). At the cutoff of 27, 25, and 9 cells/mL for EpCAM+-CTCs, TSHR+-CTCs, and PDPN+-CTCs, the accuracy of the assay was equivalent to 69.5%, 67.2%, and 68.5%, respectively. These data together indicate that CTC testing is worthy to be considered as a routine clinical test to benefit clinical care of patients with thyroid cancer. Citation Format: Ching-Ping Tseng, Jen-Der Lin, Miaw-Jene Liou, Wei-Shan Hung, Hsueh-Ling Hsu, Kong-Kit Leong, Yu-Ting Chen, Ju-Chien Cheng. Circulating tumor cells as the prognostic marker for non-remission and disease-specific mortality of patients with thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5586.