Tseng Ching-Ping, Leong Kong-Kit, Liou Miaw-Jene, Hsu Hsueh-Ling, Lin Hung-Chih, Chen Yi-An, Lin Jen-Der
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
Oncotarget. 2017 Aug 24;8(44):77453-77464. doi: 10.18632/oncotarget.20512. eCollection 2017 Sep 29.
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.
局部区域复发或远处转移通常会导致甲状腺乳头状癌(PTC)患者死亡。本研究调查了循环上皮细胞(CEC)计数是否为监测PTC治疗效果的有价值标志物。129例PTC患者在我们的医疗中心接受治疗,并根据反应情况分为4组:疗效极佳组(n = 45)、生化不完全反应组(n = 15)、不确定组(n = 37)和结构不完全反应组(n = 32)。通过PowerMag阴性选择系统从外周血中富集CEC。通过免疫荧光染色分别定义了表达上皮细胞粘附分子(EpCAM)、促甲状腺激素受体(TSHR,甲状腺细胞标志物)和血小板内皮细胞粘附分子(PDPN,PTC患者预后不良相关标志物)的三种CEC亚型。本研究纳入患者的表达EpCAM、TSHR和PDPN的CEC中位数(细胞/毫升血液)分别为23(四分位间距10 - 61)、19(四分位间距8 - 50)和8(四分位间距3 - 22)。在不受抗甲状腺球蛋白抗体干扰的情况下,不同治疗反应组患者的EpCAM - CEC、TSHR - CEC和PDPN - CEC数量存在统计学差异(P<0.0001)。与其他患者相比,结构不完全反应患者的所有三种CEC亚型计数更高。在三种CEC亚型中,EpCAM - CEC在区分疗效极佳患者和结构不完全反应患者方面表现更佳。当临界值为39个EpCAM - CEC/毫升时,该检测方法的敏感性和特异性分别为84.4%和95.6%。CEC检测可补充当前监测PTC治疗效果的标准方法。