Ippokratis Messaritakis1, Michail Nikolaou2, Eleni Politaki1, Fillipos Koinis1, Eleni Lagoudaki3, Anastasios Koutsopoulos3, Nefeli Georgoulia4, Vassilis Georgoulias5, Athanasios Kotsakis6. 1. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece. 2. Department of Internal Medicine, Hipokration General Hospital of Athens, Greece. 3. Department of Pathology, University General Hospital of Heraklion, Greece. 4. First Department of Medical Oncology, IASO General Hospital of Athens, Greece. 5. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece; First Department of Medical Oncology, IASO General Hospital of Athens, Greece. Electronic address: georgoul@med.uoc.gr. 6. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece; Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
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.
INTRODUCTION: To investigate the presence of Bcl-2+CTCs in chemotherapy-naïve SCLCpatients 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 SCLCpatients. The changes of Bcl-2+/CD45- CTCs during treatment seem to be a dynamic biomarker associated with treatment efficacy and patients' clinical outcome.
Authors: Evan N Cohen; Gitanjali Jayachandran; Hui Gao; Wei Qiao; Suyu Liu; Jianzhong He; Yawei Qiao; Luyang Yao; Steven H Lin; James M Reuben Journal: Transl Lung Cancer Res Date: 2020-10