Transcription factors zeb1, twist and snai1 in breast carcinoma

BMC Cancer

Research Article

Vesa Kataja¹  Ismo Virtanen²  Arto Mannermaa³  Veli-Matti Kosma³  Ylermi Soini³  Reijo Sironen³  Hanna Tuhkanen³  Päivi Auvinen⁴ 

[1] Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211, Kuopio, Finland;Department of Oncology, Vaasa Central Hospital, 65130, Vaasa, Finland;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, P.O. Box 1627, FI-70211, Kuopio, Finland;Department of Clinical Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211, Kuopio, Finland;Biocenter Kuopio, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland;Institute of Biomedicine/Anatomy, University of Helsinki, P.O. Box 63, FI-00014, Helsinki, Finland;

关键词: Nuclear Expression;    Mucinous Carcinoma;    Progesterone Receptor Status;    Epithelial Tumor Cell;    Stromal Compartment;   

DOI  :  10.1186/1471-2407-11-73

 received in 2010-07-13, accepted in 2011-02-16,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundEpitheliomesenchymal 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.MethodsWe 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.ResultsNuclear 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.ConclusionsExpression 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.

【 授权许可】

CC BY   
© Soini et al; licensee BioMed Central Ltd. 2011