title: Circulating tumour cells and lung microvascular tumour cell retention in patients with metastatic breast and cervical cancer.
abstract: We have shown that in up to half of the patients with metastatic breast cancer (MBC), higher numbers of circulating tumour cells (CTCs) are present in the central venous blood (CVB) compared to the peripheral venous blood (PVB), suggesting that the lungs might retain a substantial number of CTCs. Here we report the presence of tumour cell emboli (TCE) in the microvasculature of the lungs in three out of eight patients with MBC and one patient with metastatic cervical carcinoma who had markedly elevated numbers of CTCs in the blood. All these patients suffered from symptomatic dyspnoea not easily attributable to other causes. No TCE were observed in five patients with MBC and elevated CTC counts and three patients with MBC who had low CTC counts (<5/7.5 ml). To investigate whether CTCs derived from CVB or PVB exhibit different transcriptional characteristics that might explain selective CTC retention, paired CTC samples from CVB and PVB of 12 patients with advanced breast cancer were subjected to gene expression analysis of 105 genes. No significant differences in CTC gene expression were observed. Together, these data suggest that potentially clinically relevant CTC retention in the microvasculature of the lung can occur in a subset of patients with advanced metastatic breast and cervical cancer, which seems to be transcriptionally non-selectively.
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, Antwerp 2610, Belgium; Department of Oncology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium; Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium. Electronic address: dieter.peeters@gza.be.
authors.forename: Dieter J E
authors.initials: DJ
authors.lastname: Peeters
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, Antwerp 2610, Belgium; Department of Oncology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium.
authors.forename: Anja
authors.initials: A
authors.lastname: Brouwer
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, Antwerp 2610, Belgium; Department of Oncology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium.
authors.forename: Gert G
authors.initials: GG
authors.lastname: Van den Eynden
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, Antwerp 2610, Belgium.
authors.forename: Annemie
authors.initials: A
authors.lastname: Rutten
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center and Cancer Genomics Netherlands, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Onstenk
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center and Cancer Genomics Netherlands, Wytemaweg 80, Rotterdam 3015 CN, The Netherlands.
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, Antwerp 2610, Belgium; Department of Oncology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium; Department of Oncology, KU Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Van Laere
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, Antwerp 2610, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Huget
authors.affiliation: Department of Oncology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium; Department of Pathology, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.affiliation: Department of Oncology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium; Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, Antwerp 2610, Belgium; Department of Oncology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Vermeulen
authors.affiliation: Translational Cancer Research Unit, Oncology Center GZA Hospitals Sint-Augustinus, Oosterveldlaan 24, Antwerp 2610, Belgium; Department of Oncology, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium.
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Circulating tumour cells; Dyspnoea; Gene expression profiling; Metastasis biology; Pulmonary tumour cell emboli