医学
循环肿瘤细胞
内科学
免疫荧光
波形蛋白
免疫组织化学
抗体
病理
肿瘤科
临床意义
癌症
转移
免疫学
作者
Ippokratis Messaritakis,Michail Nikolaou,Fillipos Koinis,Eleni Politaki,Anastasios Koutsopoulos,Eleni Lagoudaki,Eleni-Kyriaki Vetsika,Vassilis Georgoulias,Athanasios Kotsakis
出处
期刊:Lung Cancer
[Elsevier]
日期:2019-09-01
卷期号:135: 33-39
被引量:16
标识
DOI:10.1016/j.lungcan.2019.06.025
摘要
The aim of the study was to characterize and evaluate the presence of DLL3-positive Circulating Tumor Cells (CTCs) in SCLC patients receiving front-line chemotherapy and assess their clinical relevance.Peripheral blood was obtained from treatment-naïve patients with SCLC (n = 108 patients), after one etoposide/platinum cycle (n = 68 patients) and on disease progression (n = 48 patients). Immunofluorescence staining using antibodies against the DLL3, cytokeratins (CK), CD45 and vimentin (Vim) was used for the detection and characterization of CTCs.Before treatment, 74.1% of patients had detectable DLL3+/CD45- CTCs. One-treatment cycle significantly decreased both the detection rate (p < 0.001) and the absolute number (p < 0.001) of DLL3+/CD45- CTCs. Triple immunofluorescence staining using anti-CK, anti-Vim and anti-DLL3 antibodies revealed an important CTC heterogeneity since DLL3 could be detected in Vim+, Vim-, CK+ and CK- CTCs. On disease progression, both the detection rate and the absolute number of DLL3+/CD45- CTCs were significantly increased compared to post-1st cycle values (p < 0.001 and p = 0.002, respectively). In addition, 22.7% of patients had detectable DLL3+/CD45- cells which could not be captured by the CellSearch assay. In multivariate analysis, the detection of DLL3+/CD45- CTCs at baseline was significantly associated with decreased progression-free survival (HR = 10.8; p = 0.005) whereas their detection on disease progression was associated with decreased overall survival (HR: 28.2; p = 0.016).These findings demonstrate an important heterogeneity of CTCs, based on the expression of CK, Vim and DLL3, in patients with SCLC and the changes of DLL3+/CD45- CTCs during treatment seem to be a dynamic biomarker associated with patients' clinical outcome.
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