Characterization of DLL3-positive circulating tumor cells (CTCs) in patients with small cell lung cancer (SCLC) and evaluation of their clinical relevance during front-line treatment.
Lung Cancer
; 135: 33-39, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31447000
ABSTRACT
OBJECTIVES:
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. MATERIALS ANDMETHODS:
Peripheral blood was obtained from treatment-naïve patients with SCLC (nâ¯=â¯108 patients), after one etoposide/platinum cycle (nâ¯=â¯68 patients) and on disease progression (nâ¯=â¯48 patients). Immunofluorescence staining using antibodies against the DLL3, cytokeratins (CK), CD45 and vimentin (Vim) was used for the detection and characterization of CTCs.RESULTS:
Before treatment, 74.1% of patients had detectable DLL3+/CD45- CTCs. One-treatment cycle significantly decreased both the detection rate (pâ¯<â¯0.001) and the absolute number (pâ¯<â¯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 (pâ¯<â¯0.001 and pâ¯=â¯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 (HRâ¯=â¯10.8; pâ¯=â¯0.005) whereas their detection on disease progression was associated with decreased overall survival (HR 28.2; pâ¯=â¯0.016).CONCLUSIONS:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos e Proteínas de Sinalização Intracelular
/
Carcinoma de Pequenas Células do Pulmão
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Neoplasias Pulmonares
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Proteínas de Membrana
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Células Neoplásicas Circulantes
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Grécia