Circulating Tumor Cells With Epithelial-to-mesenchymal Transition Phenotypes Associated With Inferior Outcomes in Primary Breast Cancer

Anticancer Res. 2019 Apr;39(4):1829-1837. doi: 10.21873/anticanres.13290.

Abstract

Background/aim: Circulating tumor cells (CTCs) comprise a heterogeneous population of cancer cells with different clinical and biological value. The aim of this study was to evaluate the prognostic value of CTCs with an epithelial-mesenchymal transition (EMT) phenotype in primary breast cancer (PBC) patients.

Patients and methods: This study included 427 primary breast cancer patients. RNA extracted from CD45-depleted peripheral blood mononuclear cell (PBMCs) was evaluated for the expression of EMT transcription factors (TWIST1, SNAIL1, SLUG, ZEB1) by quantitative real time polymerase chain reaction (qRT-PCR).

Results: In total, CTC EMT was detected in 77 (18.0%) patients. Patients without detectable CTC EMT in peripheral blood had significantly longer disease-free survival than patients with detectable CTC EMT. The prognostic value of CTC EMT was demonstrated in all subgroups of patients.

Conclusion: CTCs with an EMT phenotype have a prognostic value in primary breast cancer.

Keywords: Circulating tumor cells; early breast cancer; epithelial–to–mesenchymal transition.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Middle Aged
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology*
  • Nuclear Proteins / blood
  • Nuclear Proteins / genetics
  • Phenotype
  • Prospective Studies
  • Snail Family Transcription Factors / blood
  • Snail Family Transcription Factors / genetics
  • Time Factors
  • Twist-Related Protein 1 / blood
  • Twist-Related Protein 1 / genetics
  • Young Adult
  • Zinc Finger E-box-Binding Homeobox 1 / blood
  • Zinc Finger E-box-Binding Homeobox 1 / genetics

Substances

  • Nuclear Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1