Circulating Giant Tumor-Macrophage Fusion Cells Are Independent Prognosticators in Patients With NSCLC

Yariswamy Manjunath; Jonathan B. Mitchem; Kanve N. Suvilesh; Diego M. Avella; Eric T. Kimchi; Kevin F. Staveley-O'Carroll; Chelsea B. Deroche; Klaus Pantel; Guangfu Li; Jussuf T. Kaifi

doi:10.1016/j.jtho.2020.04.034

Circulating Giant Tumor-Macrophage Fusion Cells Are Independent Prognosticators in Patients With NSCLC

Yariswamy Manjunath, Jonathan B. Mitchem, Kanve N. Suvilesh, Diego M. Avella, Eric T. Kimchi, Kevin F. Staveley-O'Carroll, Chelsea B. Deroche, Klaus Pantel, Guangfu Li, Jussuf T. Kaifi^*

^*Corresponding author for this work

Surgery, Thoracic Surgery Division

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

Introduction: Various subtypes of circulating cancer-associated cells in the blood are described. A unique circulating, large, and polymorphonuclear cell with a dual epithelial and myeloid phenotype has been suggested as a tumor-macrophage fusion cell (TMF). The goal of the study was to identify the impact of distinct TMFs on survival among patients with NSCLC. Methods: In this prospective trial, 7.5 mL of whole blood sample was collected. After microfilter enrichment, immunofluorescent staining was performed, identifying TMFs as greater than or equal to 30 μm in size and dual epithelial (cytokeratin 8, 18, or 19-, or epithelial cell adhesion molecule-positive) and myeloid- or macrophage-positive (CD14- or CD45-positive) cells with at least one 4′,6-diamidino-2-phenylindole+ nucleus. Results: Circulating TMFs were identified in 88 of 115 patients (76.5%) with NSCLC (mean 3.052 [SEM ± 0.306]; median 2 [range 0–17]) but were rare in long-term smokers without cancer (6 of 87 [6.9%]; 0.081 [±0.034]; 0 [0–2]), and absent in 20 healthy controls. Comparing the presence of TMFs in patients with NSCLC versus smokers without cancer, specificity was 93.1% (95% confidence interval: 85.6–97.4%) and sensitivity 76.5% (95% confidence interval: 67.7%–83.9%). TMF counts correlated with American Joint Committee on Cancer tumor stages. More importantly, more than one TMF and giant TMFs sizes greater than or equal to 50 μm were associated with statistically significantly shorter overall and cancer-specific disease-free (p < 0.05) survival after curative resection for stage I to IIIA. Giant TMFs greater than or equal to 50 μm size were an independent survival predictor by multivariate analysis. Conclusions: Circulating, in particular, giant TMFs are associated with aggressive clinical behavior in surgically treated patients with NSCLC. The biological role of unique TMFs will need to be further investigated, as these may have a potential impact on immune responses toward cancer.

Original language	English (US)
Pages (from-to)	1460-1471
Number of pages	12
Journal	Journal of Thoracic Oncology
Volume	15
Issue number	9
DOIs	https://doi.org/10.1016/j.jtho.2020.04.034
State	Published - Sep 2020

Funding

This study is supported by a Mizzou Advantage Interdisciplinary Research Grant (MAIRG MA-18/059, University of Missouri, Columbia , MO) (Drs. Kaifi and Li). Dr. Mitchem received funding from the US Department of Veteran’s Affairs (K2BX004346-01A1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs. The funding bodies had no role in study design, collection, analysis, interpretation of data, or writing of the manuscript. The authors thank all subjects for their voluntary participation and to Blanche L. Lasta, RN for her assistance in the conduct of the trial.

Keywords

Circulating tumor cells
Fusion cells
Liquid biomarkers
Non–small cell lung cancer

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jtho.2020.04.034

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@article{70d51da90f60439ebf415f4a1212f8f8,

title = "Circulating Giant Tumor-Macrophage Fusion Cells Are Independent Prognosticators in Patients With NSCLC",

abstract = "Introduction: Various subtypes of circulating cancer-associated cells in the blood are described. A unique circulating, large, and polymorphonuclear cell with a dual epithelial and myeloid phenotype has been suggested as a tumor-macrophage fusion cell (TMF). The goal of the study was to identify the impact of distinct TMFs on survival among patients with NSCLC. Methods: In this prospective trial, 7.5 mL of whole blood sample was collected. After microfilter enrichment, immunofluorescent staining was performed, identifying TMFs as greater than or equal to 30 μm in size and dual epithelial (cytokeratin 8, 18, or 19-, or epithelial cell adhesion molecule-positive) and myeloid- or macrophage-positive (CD14- or CD45-positive) cells with at least one 4′,6-diamidino-2-phenylindole+ nucleus. Results: Circulating TMFs were identified in 88 of 115 patients (76.5%) with NSCLC (mean 3.052 [SEM ± 0.306]; median 2 [range 0–17]) but were rare in long-term smokers without cancer (6 of 87 [6.9%]; 0.081 [±0.034]; 0 [0–2]), and absent in 20 healthy controls. Comparing the presence of TMFs in patients with NSCLC versus smokers without cancer, specificity was 93.1% (95% confidence interval: 85.6–97.4%) and sensitivity 76.5% (95% confidence interval: 67.7%–83.9%). TMF counts correlated with American Joint Committee on Cancer tumor stages. More importantly, more than one TMF and giant TMFs sizes greater than or equal to 50 μm were associated with statistically significantly shorter overall and cancer-specific disease-free (p < 0.05) survival after curative resection for stage I to IIIA. Giant TMFs greater than or equal to 50 μm size were an independent survival predictor by multivariate analysis. Conclusions: Circulating, in particular, giant TMFs are associated with aggressive clinical behavior in surgically treated patients with NSCLC. The biological role of unique TMFs will need to be further investigated, as these may have a potential impact on immune responses toward cancer.",

keywords = "Circulating tumor cells, Fusion cells, Liquid biomarkers, Non–small cell lung cancer",

author = "Yariswamy Manjunath and Mitchem, {Jonathan B.} and Suvilesh, {Kanve N.} and Avella, {Diego M.} and Kimchi, {Eric T.} and Staveley-O'Carroll, {Kevin F.} and Deroche, {Chelsea B.} and Klaus Pantel and Guangfu Li and Kaifi, {Jussuf T.}",

note = "Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = sep,

doi = "10.1016/j.jtho.2020.04.034",

language = "English (US)",

volume = "15",

pages = "1460--1471",

journal = "Journal of Thoracic Oncology",

issn = "1556-0864",

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}

TY - JOUR

T1 - Circulating Giant Tumor-Macrophage Fusion Cells Are Independent Prognosticators in Patients With NSCLC

AU - Manjunath, Yariswamy

AU - Mitchem, Jonathan B.

AU - Suvilesh, Kanve N.

AU - Avella, Diego M.

AU - Kimchi, Eric T.

AU - Staveley-O'Carroll, Kevin F.

AU - Deroche, Chelsea B.

AU - Pantel, Klaus

AU - Li, Guangfu

AU - Kaifi, Jussuf T.

PY - 2020/9

Y1 - 2020/9

N2 - Introduction: Various subtypes of circulating cancer-associated cells in the blood are described. A unique circulating, large, and polymorphonuclear cell with a dual epithelial and myeloid phenotype has been suggested as a tumor-macrophage fusion cell (TMF). The goal of the study was to identify the impact of distinct TMFs on survival among patients with NSCLC. Methods: In this prospective trial, 7.5 mL of whole blood sample was collected. After microfilter enrichment, immunofluorescent staining was performed, identifying TMFs as greater than or equal to 30 μm in size and dual epithelial (cytokeratin 8, 18, or 19-, or epithelial cell adhesion molecule-positive) and myeloid- or macrophage-positive (CD14- or CD45-positive) cells with at least one 4′,6-diamidino-2-phenylindole+ nucleus. Results: Circulating TMFs were identified in 88 of 115 patients (76.5%) with NSCLC (mean 3.052 [SEM ± 0.306]; median 2 [range 0–17]) but were rare in long-term smokers without cancer (6 of 87 [6.9%]; 0.081 [±0.034]; 0 [0–2]), and absent in 20 healthy controls. Comparing the presence of TMFs in patients with NSCLC versus smokers without cancer, specificity was 93.1% (95% confidence interval: 85.6–97.4%) and sensitivity 76.5% (95% confidence interval: 67.7%–83.9%). TMF counts correlated with American Joint Committee on Cancer tumor stages. More importantly, more than one TMF and giant TMFs sizes greater than or equal to 50 μm were associated with statistically significantly shorter overall and cancer-specific disease-free (p < 0.05) survival after curative resection for stage I to IIIA. Giant TMFs greater than or equal to 50 μm size were an independent survival predictor by multivariate analysis. Conclusions: Circulating, in particular, giant TMFs are associated with aggressive clinical behavior in surgically treated patients with NSCLC. The biological role of unique TMFs will need to be further investigated, as these may have a potential impact on immune responses toward cancer.

AB - Introduction: Various subtypes of circulating cancer-associated cells in the blood are described. A unique circulating, large, and polymorphonuclear cell with a dual epithelial and myeloid phenotype has been suggested as a tumor-macrophage fusion cell (TMF). The goal of the study was to identify the impact of distinct TMFs on survival among patients with NSCLC. Methods: In this prospective trial, 7.5 mL of whole blood sample was collected. After microfilter enrichment, immunofluorescent staining was performed, identifying TMFs as greater than or equal to 30 μm in size and dual epithelial (cytokeratin 8, 18, or 19-, or epithelial cell adhesion molecule-positive) and myeloid- or macrophage-positive (CD14- or CD45-positive) cells with at least one 4′,6-diamidino-2-phenylindole+ nucleus. Results: Circulating TMFs were identified in 88 of 115 patients (76.5%) with NSCLC (mean 3.052 [SEM ± 0.306]; median 2 [range 0–17]) but were rare in long-term smokers without cancer (6 of 87 [6.9%]; 0.081 [±0.034]; 0 [0–2]), and absent in 20 healthy controls. Comparing the presence of TMFs in patients with NSCLC versus smokers without cancer, specificity was 93.1% (95% confidence interval: 85.6–97.4%) and sensitivity 76.5% (95% confidence interval: 67.7%–83.9%). TMF counts correlated with American Joint Committee on Cancer tumor stages. More importantly, more than one TMF and giant TMFs sizes greater than or equal to 50 μm were associated with statistically significantly shorter overall and cancer-specific disease-free (p < 0.05) survival after curative resection for stage I to IIIA. Giant TMFs greater than or equal to 50 μm size were an independent survival predictor by multivariate analysis. Conclusions: Circulating, in particular, giant TMFs are associated with aggressive clinical behavior in surgically treated patients with NSCLC. The biological role of unique TMFs will need to be further investigated, as these may have a potential impact on immune responses toward cancer.

KW - Circulating tumor cells

KW - Fusion cells

KW - Liquid biomarkers

KW - Non–small cell lung cancer

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Circulating Giant Tumor-Macrophage Fusion Cells Are Independent Prognosticators in Patients With NSCLC

Abstract

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UN SDGs

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