Sawayer, Elinor Jane; (2002) A molecular study of phyllodes tumours of the breast. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Phyllodes tumours are uncommon fibroepithelial mammary lesions which may show a spectrum of behaviour from benign through to sarcomatous transformation. For this study 124 paraffin embedded phyllodes tumours were collected. The epithelium and stroma were microdissected allowing analysis of each component separately. The results show that allelic imbalance can occur in both the stroma and epithelium, sometimes as independent genetic events. These findings throw into doubt the classical view that phyllodes tumours are simply stromal neoplasms and raise questions about the nature of stromal - epithelial interactions in these tumours. The HUMARA assay and FISH were used to look at the clonal origins of phyllodes tumours. These experiments suggest that the stroma and epithelium do not arise from the same malignant clone. Stromal- epithelial interactions were studied by assessing the Wnt and IGF pathways in these tumours. These experiments show that stromal proliferation in benign phyllodes tumours relies on abnormalities in these pathways which result not from mutation but from Wnt over-expression in the epithelium and IGF over-expression in the stroma. In malignant phyllodes, however, this does not appear to be the case, the stromal proliferation appears to become independent of the Wnt pathway. Further investigation of malignant tumours has been performed using immunohistochemistry, and comparative genomic hybridisation in order to try and elucidate the cause of malignant transformation in these tumours, c-myc and c-kit over-expression have been shown to be common in malignant tumours and in some cases c-myc over-expression is due to gene amplification.

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