Circulating epithelial cell counts for monitoring the therapeutic outcome of patients with papillary thyroid carcinoma

// Ching-Ping Tseng 1, 2, 3, 4 , Kong-Kit Leong 1 , Miaw-Jene Liou 5 , Hsueh-Ling Hsu 1 , Hung-Chih Lin 2 , Yi-An Chen 1 and Jen-Der Lin 5 1 Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC 2 Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC 3 Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, ROC 4 Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC 5 Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC Correspondence to: Jen-Der Lin, email: einjd@adm.cgmh.org.tw Ching-Ping Tseng, email: ctseng@mail.cgu.edu.tw Keywords: circulating epithelial cells, epithelial cell adhesion molecule, papillary thyroid carcinoma, podoplanin, therapeutic response Received: May 01, 2017     Accepted: August 08, 2017     Published: August 24, 2017 ABSTRACT 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.