Legumain expression as a prognostic factor in breast cancer patients

Abstract

Invasive tumor cells and their microenvironments are enriched with a broad spectrum of different proteases. Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of solid tumors. However, there is no data available identifying the relationship of legumain expression and clinicopathologic or biological variables in invasive breast cancer. For the first time, the prevalence of legumain expression in invasive breast cancer (n = 432) and non-neoplastic breast tissues (n = 128) was investigated by immunohistochemistry. Three staining patterns were observed in the cytoplasm: diffuse positivity, tiny dots and vesicles. Whereas vesicular positivity in the majority of tumor cells was significantly correlated to an adverse outcome, cytoplasmic and dot-like staining showed no prognostic effect. Vesicular positivity was observed in 24% of carcinomas, but only in one case of non-neoplastic breast tissue (<1%; proliferative mastopathy). This staining pattern was found to be independent of other factors analysed as grading, nodal status or HER2 expression. Besides being of prognostic value, legumain might prove to be an important predictive factor in breast cancer, since its unique cleavage specificity is already used in prodrug activation strategies.

Overexpression of asparaginyl endopeptidase is significant for esophageal carcinoma metastasis and predicts poor patient prognosis

“…AEP is reported to be overexpressed in multiple types of human solid tumors and acute lymphoblastic leukemia compared with normal tissues (16)(17)(18)(19)(20)(21). In the present study, it was demonstrated that AEP mRNA and protein levels were increased in EC109 and TE-1 esophageal cancer cell lines.…”

“…AEP has been demonstrated to contribute important functions in kidney physiology, immunity, atherogenesis and bone metabolism (9)(10)(11)(12)(13)(14)(15). In previous years, high AEP expression has been observed in a variety of solid tumors and acute lymphoblastic leukemia (16)(17)(18)(19)(20)(21). Furthermore, AEP expression positively correlated with clinicopathological and biological variables in colorectal, and breast cancer (19,20).…”

Suppression of Dendritic Cell-mediated Responses by Genes in Calcium and Cysteine Protease Pathways during Mycobacterium tuberculosis Infection

“…Senp8 is a NEDD8-specific protease that has an important role in deneddylation of cullin, a substrate for neddylation (34). In addition to playing a role during apoptosis, Lgmn, an asparaginyl endopeptidase, is overexpressed in many human solid tumors, breast, colon, and prostate cancer and sparsely expressed in normal tissues (32). Snrk is reported as a novel substrate for liver kinase B1 (29).…”

Tumor Proteomics by Multivariate Analysis on Individual Pathway Data for Characterization of Vulvar Cancer Phenotypes

“…Legumain is a cysteine protease activated by low pH, involved in the lysosomal and endosomal processing of bacterial peptides and endogenous proteins (54,55). A positive correlation between LGMN and tumor invasion and metastasis has been observed in a mouse colon cancer model (56), and LGMN is proposed as a prognostic marker in breast cancer, with positive vesicular IHC staining correlated to poor outcome (57). Further, LGMN is suggested as a marker of squamous cell nasopharyngeal carcinoma (58).…”