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Franken, André; Kraemer, Annika; Sicking, Alicia; Watolla, Meike; Rivandi, Mahdi; Yang, Liwen; Warfsmann, Jens; Polzer, Bernhard M.; Friedl, Thomas W. P.; Meier-Stiegen, Franziska; Stoecklein, Nikolas H.; Dayan, Davut; Riethdorf, Sabine; Mueller, Volkmar; Pantel, Klaus; Koch, André; Hartkopf, Andreas D.; Krawczyk, Natalia; Ruckhaeberle, Eugen; Niederacher, Dieter; Fehm, Tanja; Neubauer, Hans

Comparative analysis of EpCAM high-expressing and low-expressing circulating tumour cells with regard to their clonal relationship and clinical value

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  • Medientyp: E-Artikel
  • Titel: Comparative analysis of EpCAM high-expressing and low-expressing circulating tumour cells with regard to their clonal relationship and clinical value
  • Beteiligte: Franken, André; Kraemer, Annika; Sicking, Alicia; Watolla, Meike; Rivandi, Mahdi; Yang, Liwen; Warfsmann, Jens; Polzer, Bernhard M.; Friedl, Thomas W. P.; Meier-Stiegen, Franziska; Stoecklein, Nikolas H.; Dayan, Davut; Riethdorf, Sabine; Mueller, Volkmar; Pantel, Klaus; Koch, André; Hartkopf, Andreas D.; Krawczyk, Natalia; Ruckhaeberle, Eugen; Niederacher, Dieter; Fehm, Tanja; Neubauer, Hans
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: British Journal of Cancer, 128 (2023) 9, Seite 1742-1752
  • Sprache: Englisch
  • DOI: 10.1038/s41416-023-02179-0
  • ISSN: 0007-0920; 1532-1827
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Abstract Background Circulating tumour cells (CTCs) are mainly enriched based on the epithelial cell adhesion molecule (EpCAM). Although it was shown that an EpCAM low-expressing CTC fraction is not captured by such approaches, knowledge about its prognostic and predictive relevance and its relation to EpCAM-positive CTCs is lacking. Methods We developed an immunomagnetic assay to enrich CTCs from metastatic breast cancer patients EpCAM independently using antibodies against Trop-2 and CD-49f and characterised their EpCAM expression. DNA of single EpCAM high expressing and low expressing CTCs was analyzed regarding chromosomal aberrations and predictive mutations. Additionally, we compared CTC-enrichment on the CellSearch system using this antibody mix and the EpCAM based enrichment. Results Both antibodies acted synergistically in capturing CTCs. Patients with EpCAM high-expressing CTCs had a worse overall and progression-free survival. EpCAM high- and low-expressing CTCs presented similar chromosomal aberrations and mutations indicating a close evolutionary relationship. A sequential enrichment of CTCs from the EpCAM-depleted fraction yielded a population of CTCs not captured EpCAM dependently but harbouring predictive information. Conclusions Our data indicate that EpCAM low-expressing CTCs could be used as a valuable tumour surrogate material—although they may be prognostically less relevant than EpCAM high-expressing CTCs—and have particular benefit if no CTCs are detected using EpCAM-dependent technologies.
  • Zugangsstatus: Freier Zugang