title: Transcription factors zeb1, twist and snai1 in breast carcinoma.
abstract: BACKGROUND
  Epitheliomesenchymal transition (EMT) is the process where cancer cells attain fibroblastic features and are thus able to invade neighboring tissues. Transcriptional factors zeb1, snai1 and twist regulate EMT.
  
  
  METHODS
  We used immunohistochemistry to investigate the expression of zeb1, twist and snai1 in tumor and stromal compartments by in a large set of breast carcinomas. The results were compared with estrogen and progesterone receptor status, HER2 amplification, grade, histology, TNM status and survival of the patients.
  
  
  RESULTS
  Nuclear expression for twist was seen in the epithelial tumor cell compartment in 3.6% and for snai1 in 3.1% of the cases while zeb1 was not detected at all in these areas. In contrast, the tumor stromal compartment showed nuclear zeb1 and twist expression in 75% and 52.4% of the cases, respectively. Although rare, nuclear expression of twist in the epithelial tumor cell compartment was associated with a poor outcome of the patients (p = 0.054 log rank, p = 0.013, Breslow, p = 0.025 Tarone-Ware). Expression of snai1, or expression of zeb1 or twist in the stromal compartment did not have any prognostic significance. Furthermore, none of these factors associated with the size of the tumors, nor with the presence of axillary or distant metastases. Expression of zeb1 and twist in the stromal compartment was positively associated with a positive estrogen or progesterone receptor status of the tumors. Stromal zeb1 expression was significantly lower in ductal in situ carcinomas than in invasive carcinomas (p = 0.020). Medullary carcinomas (p = 0.017) and mucinous carcinomas (p = 0.009) had a lower stromal expression of zeb1 than ductal carcinomas. Stromal twist expression was also lower in mucinous (p = 0.017) than in ductal carcinomas.
  
  
  CONCLUSIONS
  Expression of transcriptional factors zeb1 and twist mainly occur in the stromal compartment of breast carcinomas, possibly representing two populations of cells; EMT transformed neoplastic cells and stromal fibroblastic cells undergoing activation of zeb1 and twist due to growth factors produced by the tumor. However, epithelial expression of twist was associated with a poor prognosis, hinting at its importance in the spread of breast carcinoma.
authors.affiliation: Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, School of Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland. ylermi.soini@uef.fi
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Hanna
authors.initials: H
authors.lastname: Tuhkanen
authors.forename: Reijo
authors.initials: R
authors.lastname: Sironen
authors.forename: Ismo
authors.initials: I
authors.lastname: Virtanen
authors.forename: Vesa
authors.initials: V
authors.lastname: Kataja
authors.forename: Päivi
authors.initials: P
authors.lastname: Auvinen
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000378:metabolism* / Q000502:physiology; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1