title: Beta-catenin abnormalities and associated insulin-like growth factor overexpression are important in phyllodes tumours and fibroadenomas of the breast.
abstract: The aim of this study was to assess the expression of IGF-I and IGF-II in phyllodes tumours and fibroadenomas and to see if there is any correlation between nuclear beta-catenin expression and IGF-I and IGF-II expression in these tumours. In a previous study, it has been shown that Wnt signalling is important in the pathogenesis of phyllodes tumours of the breast. Epithelial Wnt5a overexpression and stromal Wnt2 overexpression were associated with abnormal, nuclear localization of beta-catenin in the stromal cells of these tumours. However, not all tumours with beta-catenin accumulation showed Wnt overexpression. One other possible cause of beta-catenin accumulation is overexpression of insulin-like growth factors (IGFs), as both IGF-I and IGF-II have been shown to stabilize beta-catenin. In this study, 30 fibroadenomas of the breast were assessed for beta-catenin expression using immunohistochemistry and the results were compared with previous data from 119 phyllodes tumours. In situ hybridization was used to assess IGF-I and IGF-II expression in 23 phyllodes tumours and 16 fibroadenomas. Nineteen phyllodes tumours (83%) showed widespread overexpression of IGF-II and 5/23 (22%) showed widespread overexpression of IGF-I. IGF-I expression correlated with nuclear beta-catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF-I expression. There was a degree of nuclear beta-catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear beta-catenin staining correlated with IGF-I overexpression. Extensive IGF-II overexpression was also found in the majority of fibroadenomas (12/16). These results support the hypothesis that IGF-I and IGF-II overexpression may be important in the pathogenesis of fibroepithelial neoplasms of the breast and that IGF-I overexpression is likely to be contributing to the nuclear beta-catenin localization observed in the tumours.
authors.affiliation: Molecular and Population Genetics Laboratory, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. elinor.sawyer@cancer.org.uk
authors.forename: Elinor J
authors.initials: EJ
authors.lastname: Sawyer
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hanby
authors.forename: Richard
authors.initials: R
authors.lastname: Poulsom
authors.forename: Rosemary
authors.initials: R
authors.lastname: Jeffery
authors.forename: Cheryl E
authors.initials: CE
authors.lastname: Gillett
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Paul
authors.initials: P
authors.lastname: Ellis
authors.forename: Ian P M
authors.initials: IP
authors.lastname: Tomlinson
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D018226:Fibroadenoma / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D003557:Phyllodes Tumor / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D013002:Somatomedins; D015534:Trans-Activators; D051176:beta Catenin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II