title: 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.
abstract: The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, 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.
authors.affiliation: Northern Institute for Cancer Research, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; Department of Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt.
authors.forename: Ahmed R H
authors.initials: ARH
authors.lastname: Ahmed
authors.affiliation: Breast Cancer Unit, Department of Surgery, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Griffiths
authors.affiliation: Northern Institute for Cancer Research, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tilby
authors.affiliation: Northern Institute for Cancer Research, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; Department of Pathology, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Westley
authors.affiliation: Northern Institute for Cancer Research, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; Department of Pathology, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom. Electronic address: F.E.B.May@ncl.ac.uk.
authors.forename: Felicity E B
authors.initials: FEB
authors.lastname: May
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D010641:Phenotype; D000071165:Trefoil Factor-3; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D010455:Peptides; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3