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

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Abstract

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.

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Acknowledgments

Thelma Mäkikyrö foundation (PK), The Orion-Farmos Foundation (PK), The Cancer Society of Finland (PK), The Finnish Anti-tuberculosis Association (YS), Special Government Funding of Kuopio University Hospital (PA) and Cancer Center of University of Eastern Finland (PA, YS) and The Finnish Cultural Foundation are acknowledged for their financial support.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology and Radiotherapy, Oulu University Hospital, P.O. Box 22, 90029, Oulu, Finland

    Peeter Karihtala & Arja Jukkola-Vuorinen

  2. Department of Oncology, Cancer Center of Eastern Finland, Kuopio University Hospital, Kuopio, Finland

    Päivi Auvinen

  3. Department of Pathology, Oulu University Hospital, Oulu, Finland

    Saila Kauppila & Kirsi-Maria Haapasaari

  4. Department of Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland

    Ylermi Soini

Authors
  1. Peeter Karihtala
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  2. Päivi Auvinen
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  4. Kirsi-Maria Haapasaari
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Correspondence to Peeter Karihtala.

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Karihtala, P., Auvinen, P., Kauppila, S. et al. 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 138, 81–90 (2013). https://doi.org/10.1007/s10549-013-2442-0

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  • DOI: https://doi.org/10.1007/s10549-013-2442-0

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