Pathogenic mechanisms in the initiation and progression of mammary phyllodes tumours

Mammary phyllodes tumours (PTs) are rare fibroepithelial neoplasms of the breast. They have a propensity to recur locally and the ability to metastasise. There is some correlation between the histological parameters of PTs and their biological behaviour; however, no single feature or grading scheme can accurately predict the behaviour of a PT. The PTs that will recur and/or metastasise are not being precisely delineated with the currently available diagnostic tools. A number of pathways/markers have been implicated in the pathogenesis of PTs including hormone receptors, members of the Wnt pathway, cell cycle proteins, factors involved in angiogenesis, tyrosine kinase receptors and matrix metalloproteases. The currently available evidence supports a model where initiation of PTs involves interactions between the epithelium and stroma and these interactions are lost with the progression to malignancy such that growth of the stroma becomes autonomous of the epithelium. Loss of the stromal-epithelial interdependancy, increased stromal proliferation, angiogenesis and matrix alterations appear to be involved in the progression to malignancy.