Vimentin, zeb1 and Sip1 are up-regulated in triple-negative and basal-like breast cancers: association with an aggressive tumour phenotype

Breast Cancer Res Treat. 2013 Feb;138(1):81-90. doi: 10.1007/s10549-013-2442-0. Epub 2013 Feb 15.


In epithelial-to-mesenchymal transition (EMT) epithelial cancer cells achieve mesenchymal features, essentially helping them to metastasize. There is some evidence that EMT could be increased in triple-negative (TNBC) or basal-like breast cancers, although more precise mechanisms considering e.g. EMT-regulating transcription factors are largely unknown. We assessed immunohistochemically vimentin (separately in in situ areas and in invasive cells) as an indicator of EMT, and also EMT-regulating transcription factors zeb1 (separately in stroma and tumour) and Sip1 (in nuclei and cytoplasm) in histological samples of 231 women with local or locally advanced invasive breast cancer. 51.1 % of patients had TNBC and 48.9 % oestrogen and progesterone receptor-positive and HER2 negative breast cancer. Basal-like breast cancers were defined as TNBC that also expressed epidermal growth factor receptor EGFR and/or cytokeratin 5/6. Vimentin expression in invasive cells was higher in TNBCs (p = 9 × 10(-12)) compared to non-TNBC tumours. Vimentin (p = 2 × 10(-6)), nuclear Sip1 (p = 0.035) and zeb1 in stroma (p = 0.013) were overexpressed in basal-like cancers compared to non-basal-like TNBCs. In non-TNBC group findings between studied markers and clinicopathological factors were rare. However, in TNBC cases, vimentin expression in invasive cells associated with poor differentiation (p = 0.00007), zeb1 expression in cancer cells with higher grade (p = 0.002), vascular invasion (p = 0.036) and larger T-class (p = 0.027), whereas stromal zeb1 associated with lymphatic vessel invasion (p = 0.036) and vascular invasion (p = 0.039). High nuclear Sip1 expression was prognostic for poor disease-free survival (p = 0.002) in the whole cohort. The current results emphasize the increased role of EMT in TNBC and especially in basal-like breast cancers. These observations also support the role of studied parameters in tumour progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Disease Progression
  • Female
  • Homeodomain Proteins / metabolism*
  • Humans
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasms, Basal Cell / metabolism*
  • Neoplasms, Basal Cell / mortality
  • Neoplasms, Basal Cell / pathology
  • Nerve Tissue Proteins / metabolism*
  • Phenotype
  • Prognosis
  • RNA-Binding Proteins / metabolism*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Transcription Factors / metabolism*
  • Up-Regulation*
  • Vimentin / metabolism*
  • Zinc Finger E-box-Binding Homeobox 1


  • GEMIN2 protein, human
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Transcription Factors
  • Vimentin
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • Receptor, ErbB-2