β‐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 β‐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 β‐catenin in the stromal cells of these tumours. However, not all tumours with β‐catenin accumulation showed Wnt overexpression. One other possible cause of β‐catenin accumulation is overexpression of insulin‐like growth factors (IGFs), as both IGF‐I and IGF‐II have been shown to stabilize β‐catenin. In this study, 30 fibroadenomas of the breast were assessed for β‐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 β‐catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF‐I expression. There was a degree of nuclear β‐catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear β‐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 β‐catenin localization observed in the tumours. Copyright © 2003 John Wiley & Sons, Ltd.