title: Vimentin, zeb1 and Sip1 are up-regulated in triple-negative and basal-like breast cancers: association with an aggressive tumour phenotype.
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.
authors: Department of Oncology and Radiotherapy, Oulu University Hospital, PO Box 22, 90029 Oulu, Finland. peeter.karihtala@oulu.fi
authors: Peeter
authors: P
authors: Karihtala
authors: Päivi
authors: P
authors: Auvinen
authors: Saila
authors: S
authors: Kauppila
authors: Kirsi-Maria
authors: KM
authors: Haapasaari
authors: Arja
authors: A
authors: Jukkola-Vuorinen
authors: Ylermi
authors: Y
authors: Soini
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018295:Neoplasms, Basal Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; D014746:Vimentin; D000071799:Zinc Finger E-box-Binding Homeobox 1; C108381:GEMIN2 protein, human; C486307:ZEB1 protein, human