Legumain is a
proteolytic enzyme that plays a role in the regulation of cell proliferation in invasive
breast cancer. Studies evaluating its role in
ductal carcinoma in situ (
DCIS) are lacking. Here, we aimed to characterize
legumain protein expression in
DCIS and evaluate its prognostic significance.
Legumain was assessed immunohistochemically in a tissue microarray of a well-characterized cohort of
DCIS (n = 776 pure
DCIS and n = 239
DCIS associated with invasive
breast cancer (
DCIS-mixed)).
Legumain immunoreactivity was scored in
tumor cells and surrounding stroma and related to clinicopathological parameters and patient outcome. High
legumain expression was observed in 23% of pure
DCIS and was associated with features of high-risk
DCIS including higher nuclear grade, comedo
necrosis,
hormone receptor negativity, HER2 positivity, and higher proliferation index.
Legumain expression was higher in
DCIS associated with invasive
breast cancer than in pure
DCIS (p < 0.0001). In the
DCIS-mixed cohort, the invasive component showed higher
legumain expression than the
DCIS component (p < 0.0001).
Legumain was an independent predictor of shorter local recurrencefree interval for all recurrences (p = 0.0003) and for invasive recurrences (p = 0.002). When incorporated with other risk factors,
legumain provided better patient risk stratification. High
legumain expression is associated with poor prognosis in
DCIS and could be a potential marker to predict
DCIS progression to invasive disease.