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TFF3 Is a Normal Breast Epithelial Protein and Is Associated with Differentiated Phenotype in Early Breast Cancer but Predisposes to Invasion and Metastasis in Advanced Disease

Lookup NU author(s): Ahmed Ahmed, Andrew Griffiths, Professor Bruce Westley, Dr Felicity May



The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogencsis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination. (Am J Pathol 2012, 180:904-916; DOI:10.10164/j.ajpath.2011.11.022)

Publication metadata

Author(s): Ahmed ARH, Griffiths AB, Tilby MT, Westley BR, May FEB

Publication type: Article

Publication status: Published

Journal: American Journal of Pathology

Year: 2012

Volume: 180

Issue: 3

Pages: 904-916

Print publication date: 01/03/2012

Online publication date: 15/02/2012

Acceptance date: 17/11/2011

Date deposited: 24/04/2015

ISSN (print): 0002-9440

ISSN (electronic): 1525-2191

Publisher: Elsevier Inc.


DOI: 10.1016/j.ajpath.2011.11.022


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