Toss MS, et al. - Researchers in this investigation characterized the expression of cathepsin A (CTSA), a key regulatory enzyme for galactoside metabolism, protein in ductal carcinoma in situ (DCIS) and assessed its prognostic significance. A large DCIS cohort [n = 776 for pure DCIS and n = 239 for DCIS related to IBC (DCIS/IBC)] prepared as a tissue microarray was immunohistochemically stained for CTSA. In 48% of pure DCIS, high CTSA expression was observed. Findings revealed that high expression was related to poor DCIS prognosis characteristics, including younger diagnostic age (<50 years), higher nuclear grade, hormone receptor negativity, HER2 positivity, high proliferative index and high hypoxia inducible factor 1 alpha expression. A shorter recurrence-free interval (RFI) was associated with high CTSA expression. CTSA was an independent predictor of shorter RFI in multivariate survival analysis for patients treated with breast conserving surgery. Overall, the investigators concluded that CTSA is not only associated with aggressive behaviour and poor DCIS outcome but is also a potential marker for predicting co-existing DCIS invasion.