Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Crete, Greece.
Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
Sci Rep. 2017 Mar 28;7:45351. doi: 10.1038/srep45351.
The aim of the study was to evaluate the phenotypic CTCs heterogeneity (TTF-1 and/or CD56) in SCLC patients and correlate it with the CellSearch. Peripheral blood was obtained from 108 consecutive patients. CTCs were detected by CellSearch and double-immunofluorescence using anti-CD45, anti-TTF-1 and anti-CD56 antibodies. Before chemotherapy TTF-1/CD45, CD56/CD45 and TTF-1/CD56 CTCs were detected in 66(61.1%), 55(50.9%) and 46(42.6%) patients, respectively; 60.2% of patients were CellSearch. Among the 22 patients with 0 CTCs/7.5 ml on CellSearch, TTF-1/CD45, CD56/CD45 and TTF-1/CD56 CTCs were detected in 8(36.4%), 6(27.3) and 6(27.3%) patients, respectively; no CK/EpCAM or TTF1/EpCAM CTCs were detected in these patients. One-chemotherapy cycle decreased both the number of positive patients (p < 0.001) and their CTC number (p < 0.001), irrespectively of their phenotype and the detection method. The incidence and number of the different CTC subpopulations on PD, was significantly increased at their baseline levels. Multivariate analysis revealed that the increased number of CTCs at baseline and on PD were significantly associated with decreased PFS (p = 0.048) and OS (p = 0.041), respectively. There is an important CTC heterogeneity in such patients according to the expression of TTF-1 and CD56 which could detect EpCAM CTC subpopulations and, thus, undetectable by CellSearch. These CTC subpopulations are dynamically correlated with treatment efficacy and disease-progression.
本研究旨在评估小细胞肺癌（SCLC）患者表型 CTC 异质性（TTF-1 和/或 CD56），并将其与 CellSearch 相关联。从 108 例连续患者中获得外周血。使用抗 CD45、抗 TTF-1 和抗 CD56 抗体通过 CellSearch 和双重免疫荧光法检测 CTCs。在化疗前，分别在 66（61.1%）、55（50.9%）和 46（42.6%）患者中检测到 TTF-1/CD45、CD56/CD45 和 TTF-1/CD56 CTCs；60.2%的患者为 CellSearch。在 22 例 CellSearch 检测到 0 个 CTC/7.5ml 的患者中，分别在 8（36.4%）、6（27.3）和 6（27.3%）患者中检测到 TTF-1/CD45、CD56/CD45 和 TTF-1/CD56 CTCs；这些患者未检测到 CK/EpCAM 或 TTF1/EpCAM CTCs。一个化疗周期降低了阳性患者的数量（p<0.001）及其 CTC 数量（p<0.001），而与表型和检测方法无关。PD 时不同 CTC 亚群的发生率和数量在基线水平上显著增加。多变量分析显示，基线和 PD 时 CTC 数量的增加与 PFS（p=0.048）和 OS（p=0.041）的降低显著相关。根据 TTF-1 和 CD56 的表达，此类患者存在重要的 CTC 异质性，可检测到 EpCAM CTC 亚群，而 CellSearch 无法检测到。这些 CTC 亚群与治疗效果和疾病进展密切相关。
