Circulating epithelial cells as potential biomarkers for detection of recurrence in patients of papillary thyroid carcinoma with positive serum anti-thyroglobulin antibody

Abstract

Background: Serum thyroglobulin (Tg) is not a reliable tumor marker for monitoring disease status after treatment in patients with papillary thyroid carcinoma (PTC) with positive anti-thyroglobulin antibody (TgAb). The aim of this study was to evaluate the clinical role of circulating epithelial cells (CECs) in PTC patients with positive serum TgAb and undetectable serum Tg.

Methods: A pilot study was performed to evaluate CECs in 25 PTC patients with positive serum TgAb and undetectable serum Tg. CECs were isolated and enriched from peripheral blood with a negative selection system PowerMag. Immunofluorescence staining with anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-thyroid stimulating hormone receptor (anti-TSHR) antibodies were used to define EpCAM⁺-CECs and TSHR⁺-CECs. After CECs testing, 25 patients were classified into two groups: recurrence group (n=7) and remission group (n=18) based on biopsy or imaging studies. The diagnostic accuracy and cutoff points of EpCAM⁺-CECs and TSHR⁺-CECs were evaluated using receiver operating characteristic (ROC) curves. The optimal cut-off values of CECs were determined by the Youden index (sensitivity+specificity-1).

Results: The median numbers of EpCAM⁺-CECs (72.5 vs. 10.75) and TSHR⁺-CECs (54 vs. 5.25) were significantly increased in recurrence group compared to remission group. The area under the curve (AUC) showed good performance of EpCAM⁺-CECs (0.937) and TSHR⁺-CECs (0.825) to discriminate between recurrence and remission. The cut-off value for EpCAM⁺-CECs and TSHR⁺-CECs were set at 48cells/ml and 10cells/ml, respectively and showed a sensitivity (EpCAM⁺-CECs: 85.7%; TSHR⁺-CECs: 85.7%) and a specificity (EpCAM⁺-CECs: 100%; TSHR⁺-CECs: 77.8%) in predicting the recurrence.

Conclusions: Our study suggests CECs testing could be a potential biomarker to identify recurrence in PTC patients with positive serum TgAb and undetectable serum Tg.

Keywords: Anti-thyroglobulin antibody; Circulating epithelial cells; Papillary thyroid carcinoma; Potential biomarker; Recurrence.