Characterizing the Role of Podocalyxin in Breast Carcinoma

Lymphatic invasion (LVI), the presence of tumour emboli within the peritumoural lymphatics of the breast, is an independent prognostic marker for axillary node negative breast cancer. Podocalyxin (PODXL) was the most differentially expressed protein between LVI+ and LVI- tumours in our cohort. Paradoxically, PODXL correlated with increased long term disease free survival as well as poor prognosis characteristics such as large tumour size. This thesis studied the effect of PODXL overexpression using in vitro techniques. In EpH4 three dimensional cultures, PODXL conferred resistance to TGF-β induced acinar collapse. Immunofluorescent staining of PODXL and cell polarity marker Scribble indicated loss of cell polarity in collapsed acini. Immunofluorescent staining of EMT markers showed that a classical EMT response is not the cause of the acinar collapse observed. This acinar architecture maintenance function of PODXL may be a potential component by which PODXL overexpression may be protective as is suggested by our cohort.M.Sc