Identification of Circulating Tumor Cell Phenotype in Differentiated Thyroid Carcinoma

Abstract

Objective: Circulating tumor cells (CTCs) have been considered as the origin of tumor metastasis and recurrence, which always indicate a poor prognosis. There are three phenotypes of CTCs according on different epithelial-to-mesenchymal transition (EMT) markers, including epithelial, mesenchymal, and epithelial/mesenchymal (mixed phenotypic) CTCs. We intended to explore the relationship among CTC phenotypes and the clinicopathological characteristics of patients with differentiated thyroid carcinoma (DTC). Methods: Peripheral blood samples from 58 patients with DTC were collected, and CTCs were isolated by cell sizes. To identify phenotypes of CTCs, branched DNA signal amplification technology was adopted to capture and amplify target sequences, and then multiplex RNA-in situ hybridization (RNA-ISH) assay was used to identify CTC phenotypes depended on epithelial-mesenchymal transition (EMT) markers. Results: The positive rate of CTCs was 77.59% in 58 DTC patients. Totally, 488 CTCs with detective phenotype were found. Among them, there were 121 (24.80%) epithelial CTCs, 67 (13.72%) mesenchymal CTCs, and 300 (61.48%) mixed phenotypic CTCs. An obvious increased epithelial CTCs was observed in male patients compared with female. Notably, CTCs were more prevailing in younger male patients with ETI and bilateral focus. Conclusions: The CTCs are common in DTC patients, and mixed phenotypic is the major phenotype, indicating that EMT is prevalent in DTC even though its prognosis was better than other epithelial tumors. Detection of CTC and its phenotypes might independently predict the prognosis of DTC.