Bcl-2 expression in circulating tumor cells (CTCs) of patients with small cell lung cancer (SCLC) receiving front-line treatment.
Lung Cancer
; 124: 270-278, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30268472
ABSTRACT
INTRODUCTION:
To investigate the presence of Bcl-2+CTCs in chemotherapy-naïve SCLC patients and their clinical relevance during front-line treatment.METHODS:
Peripheral blood was obtained from 66 consecutive-patients before chemotherapy administration, after one-cycle and at relapse. CTCs were detected by CellSearch and immunofluorescence using anti-Bcl-2, anti-M30, anti-cytokeratins(CK), anti-CD45 and anti-vimentin(Vim) antibodies.RESULTS:
Before treatment, CTCs were detected in 62.1% and 72.7% of patients using the CellSearch and immunofluorescence (Bcl-2+/CD45-), respectively. One-treatment cycle significantly decreased both CTCs' detection rate(p < 0.001) and their absolute number (p < 0.001). On relapse, both the number of positive-patients and the absolute number of CTC subpopulations were significantly increased, compared to post-1st cycle (CellSearch p = 0.002 and immunofluorescence p < 0.001). Immunofluorescence revealed an important CTC heterogeneity (Bcl2+/Vim+, Bcl2+/Vim-, Bcl2+/CK+, Bcl2+/CK- and Bcl2+/M30- CTCs). Moreover, 50.0% of patients without detectable CTCs by CellSearch had detectable Bcl-2+/CD45- cells. Multivariate analysis revealed a significant association between Bcl-2+/CD45-cells at baseline and PFS (HR = 4.5;p = 0.005) and OS (HR 4.3; p = 0.001). Bcl-2+/CD45-cells after one-treatment cycle were significantly associated with shorter OS (HR 13.9; p = 0.007).CONCLUSIONS:
These results demonstrate an important phenotypic CTCs heterogeneity based on the co-expression of Bcl-2, CK, Vim and M30 in SCLC patients. The changes of Bcl-2+/CD45- CTCs during treatment seem to be a dynamic biomarker associated with treatment efficacy and patients' clinical outcome.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Pequenas
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Proteínas Proto-Oncogênicas c-bcl-2
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Neoplasias Pulmonares
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Células Neoplásicas Circulantes
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Grécia