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

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

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.

Bibliografische Daten

OriginalspracheEnglisch
ISSN0007-0920
DOIs
StatusVeröffentlicht - 05.2023

Anmerkungen des Dekanats

© 2023. The Author(s).

PubMed 36823365