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.

Highlights

  • Thyroid cancer is the most common endocrine malignancy and is the fourth and the fifth most common cancer in women worldwide and in Taiwan, respectively [1,2,3]

  • Three subtypes of circulating epithelial cells (CECs) expressing epithelial cell adhesion molecule (EpCAM), thyroidstimulating hormone receptor (TSHR, a marker for thyroid cells), and podoplanin (PDPN, a marker related to poor prognosis in patients with papillary thyroid carcinoma (PTC)) were defined by immunofluorescence staining, respectively

  • A structural incomplete response may lead to additional treatment or ongoing observation depending on multiple clinico-pathological factors such as the tumor size, location, rate of growth, radioactive iodine (RAI) avidity, F-18fluorodeoxyglucose avidity, and the specific pathology of the structural lesions

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Summary

Introduction

Thyroid cancer is the most common endocrine malignancy and is the fourth and the fifth most common cancer in women worldwide and in Taiwan, respectively [1,2,3]. Patients with macroscopic invasion of tumor into the perithyroidal soft tissues (gross extrathyroidal extension), incomplete tumor resection, distant metastases, postoperative serum thyroglobulin (Tg) suggestive of distant metastases, pathologic N1 with any metastatic lymph node 3 cm in largest dimension, or follicular thyroid cancer with extensive vascular invasion (> 4 foci of vascular invasion) were defined as high risk group in thyroid cancer [8]. Postoperative patients are reclassified into four response to therapy groups which include excellent response, biochemical incomplete response, indeterminate response, and structural incomplete response based on the outcome of medical imaging and the serum level of Tg [8]. About 50-85% of the patients with a structural incomplete response continue to have persistent disease after multiple postoperative RAI therapy.

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