Significance of tumour vessel invasion in determining the morphology of isolated tumour cells in the pulmonary vein in non-small-cell lung cancer

Funaki, Soichiro; Sawabata, Noriyoshi; Abulaiti, Abulimiti; Nakagiri, Tomoyuki; Shintani, Yasushi; Inoue, Masayoshi; Minami, Masato; Okumura, Meinoshin

doi:10.1093/ejcts/ezs553

Cited by 20 publications

(15 citation statements)

References 14 publications

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“…Similar to single migratory mesenchymal-like CTCs, CTMs appear to be enriched in mesenchymal markers, an indicator of increased potential plasticity, which in turn seems to be related to more aggressive behavior, thus supporting their role in both tumor cell dissemination and the initiation of metastatic outgrowth (38,(42)(43)(44). The presence of CTMs has been reported as a negative prognostic factor in lung cancer patients (38,40,45).…”

Section: Ctcsmentioning

confidence: 78%

Circulating tumor cells versus circulating tumor DNA in lung cancer—which one will win?

Calabuig¹,

Jantus‐Lewintre²,

Herreros‐Pomares³

et al. 2016

Transl. Lung Cancer Res.

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Liquid biopsies appear to be a reliable alternative to conventional biopsies that can provide both precise molecular data useful for improving the clinical management of lung cancer patients as well as a less invasive way of monitoring tumor behavior. These advances are supported by important biotechnological developments in the fields of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Analysis of CTCs and ctDNA may be useful in treatment selection, for response monitoring, and in studying resistance mechanisms. This review focuses on the most recent technological achievements and the most relevant clinical applications for lung cancer patients in the CTC and ctDNA fields, highlighting those that are already (or are close to) being implemented in daily clinical practice.

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Section: Ctcsmentioning

confidence: 78%

Circulating tumor cells versus circulating tumor DNA in lung cancer—which one will win?

Calabuig¹,

Jantus‐Lewintre²,

Herreros‐Pomares³

et al. 2016

Transl. Lung Cancer Res.

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“…CTC clusters have been shown to be associated with poor prognosis (20,27). It is also believed that the cells within clusters can escape cell death (28).…”

Section: Resultsmentioning

confidence: 99%

“…Similar studies have been previously undertaken (16,17,19,21,22,39–41) in different cancers wherein different anatomical sources were investigated for CTCs. Morphological and molecular heterogeneity were observed in lung CTCs recovered from peripheral and pulmonary vein blood (20,28). While reinforcing these heterogeneities, our study also involves genomic profiling through RT-qPCR and mutational analysis, and long-term monitoring of patients with CTC clusters present, as they could have potential prognostic value (27).…”

Section: Discussionmentioning

confidence: 99%

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Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers

et al. 2017

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Early detection of metastasis can be aided by circulating tumor cells (CTCs), which also show potential to predict early relapse. Due to the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared to pre-operative Pe (p<0.0001) and intra-operative Pe (p<0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long term surveillance indicated that presence of clusters in pre-operative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence.

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“…[15] As such, isolated tumor cells (ITC), surrogates of CTC, were extracted from pulmonary vein blood, revealing that detecting ITC/CTC was an indicator of early recurrence; the presence of cluster ITC/CTC indicated wrong prognosis, using the EpCAM positive selection method [21] or the CD45 negativedepression gravity method [RosettSep ® (Stemcell Technologies, Vancouver, Canada)]. [22][23][24] As the sensitivity of such CTC detecting methods was not greater, the sample used pulmonary vein blood, because it contains more ITC/CTC than the peripheral circulating blood. [24] Size selection methods [ISET ® (Rarecells Diagnostics, Paris, France) and ScreenCell ® Cyto] are highly sensitive for cluster CTC, and therefore the sampling of CTC extraction using size selection methods can use peripheral blood.…”

Section: Discussionmentioning

confidence: 99%

Lung cancer biopsy dislodges tumor cells into circulating blood

Sawabata¹,

Kitamura²,

Nitta³

et al. 2017

JCMT

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Aim:A "seed" of lung cancer metastasis is circulating tumor cells (CTCs), which may be dislodged from a tumor during biopsy. This possibility was assessed among patients who underwent lung tumor biopsy using flexible fiber-topic bronchoscopy (FFB). Methods: The study involved six patients with non-small cell lung cancer who underwent FFB biopsy to diagnose a lesion pathologically (5 males and 1 female, median age 63 years, 6 adenocarcinomas, of 4 clinical-stage IA, 1 stage IB, and 1 stage IIIA), CTCs were extracted from the peripheral vein blood at pre-FFB and at post-FFB using a size selection method. Results: No tumor cell was detected at pre-and post-FFB was in three cases (50%); no tumor cells were detected pre-FFB while CTCs were detected at post-FFB in two cases (33.3%); and CTCs were detected at pre-FFB with numerous CTCs detected at post-FFB in one case (17.7%). In addition, similar tendencies were observed in each analysis of singlecell and clustered-cell categories. Conclusion: These results suggest that a FFB biopsy of lung cancer may potentially dislodge CTCs from a tumor into the circulating peripheral blood. Key words:Lung cancer, biopsy, circulating tumor cells ABSTRACTArticle history:

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Significance of tumour vessel invasion in determining the morphology of isolated tumour cells in the pulmonary vein in non-small-cell lung cancer

Abstract: Clustered ITCs were shown to be a prognostic indicator and strongly related to BVI. Our results suggest that determination of BVI has prognostic value, as clustered ITCs with metastatic potential are disseminated from the invaded vein.

Cited by 20 publications

References 14 publications

Circulating tumor cells versus circulating tumor DNA in lung cancer—which one will win?

Circulating tumor cells versus circulating tumor DNA in lung cancer—which one will win?

Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers

Lung cancer biopsy dislodges tumor cells into circulating blood

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