Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer

Cancer Lett. 2015 Jun 28;362(1):36-44. doi: 10.1016/j.canlet.2015.03.020. Epub 2015 Mar 19.

Abstract

Before using circulating tumor cells (CTCs) as liquid biopsy, insight into molecular discrepancies between CTCs and primary tumors is essential. We characterized CellSearch-enriched CTCs from 62 metastatic breast cancer (MBC) patients with ≥5 CTCs starting first-line systemic treatment. Expression levels of 35 tumor-associated, CTC-specific genes, including ESR1, coding for the estrogen receptor (ER), were measured by reverse transcription quantitative polymerase chain reaction and correlated to corresponding primary tumors. In 30 patients (48%), gene expression profiles of 35 genes were discrepant between CTCs and the primary tumor, but this had no prognostic consequences. In 15 patients (24%), the expression of ER was discrepant. Patients with ER-negative primary tumors and ER-positive CTCs had a longer median TTS compared to those with concordantly ER-negative CTCs (8.5 versus 2.1 months, P = 0.05). From seven patients, an axillary lymph node metastasis was available. In two patients, the CTC profiles better resembled the lymph node metastasis than the primary tumor. Our findings suggest that molecular discordances between CTCs and primary tumors frequently occur, but that this bears no prognostic consequences. Alterations in ER-status between primary tumors and CTCs might have prognostic implications.

Keywords: CellSearch; Circulating tumor cells; Estrogen receptor; Gene expression; Metastatic breast cancer; Prognostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Receptors, Estrogen / genetics
  • Retrospective Studies
  • Transcriptome

Substances

  • Receptors, Estrogen