The High Expression of Legumain in Canine Neoplasms: A Retrospective Analysis of 100 Cases

SIMPLE SUMMARY: Cancer is the leading cause of death in humans and is one of the most common canine diseases. The similarities in pathological features and tumor behaviors between spontaneous canine tumors and their human counterparts make dogs ideal models for comparative cancer research. Legumain is a novel asparaginyl endopeptidase that is overexpressed in numerous types of human tumors. Furthermore, legumain-targeted cancer therapy has been proposed, and the treatment efficacy is well-tolerated. Previous studies have shown that legumain regulates extracellular matrix degradation and triggers the invasion and the metastasis of tumors. However, in dogs, the role of legumain in the progression of tumors remains largely unknown, and few investigations have described the expression levels of this protein in canine tumors. The present study was carried out to evaluate whether legumain is expressed in ten different types of canine neoplasms. We found that heightened signals of legumain were expressed in all canine tumor samples in the study, and, notably, the non-mesenchymal types of tumors harbored relatively high expression levels. This study is the first to describe the legumain distribution pattern in a series of canine tumors. Though further investigation is needed, the current study has provided large-scale pan-screening data on legumain as a potential biomarker, or a therapeutic target, in veterinary oncology. ABSTRACT: Legumain, a novel asparaginyl endopeptidase, has been observed to be overexpressed in several types of human solid tumors. Elevated levels of legumain are found in human cancers, and this oncoprotein may facilitate tumor invasion and metastasis when overexpressed. These findings suggest that legumain plays a malignant role in cancer biology. However, currently, no publications have identified the role of legumain in the development of canine cancers. The present study first compared the expression patterns of legumain in paraffin-embedded canine tumor tissues, with those of normal tissues, by immunohistochemistry. A total of 100 canine tumor samples, including mast cell tumors, soft tissue sarcoma, hemangiosarcoma, lymphoma, mammary gland carcinoma, hepatoid gland tumor, squamous cell carcinoma, trichoblastoma, and melanoma were evaluated. Compared with the normal tissues, all tumor samples displayed high intensities of legumain expression. Mesenchymal-type tumors displayed immunoreactivity for legumain, with an average expression of 40.07% ± 1.70%, which was significantly lower than those of epithelial tumors and other types of tumors, which had median expressions of 49.12% ± 1.75% and 47.35% ± 2.71%, respectively (p < 0.05). These findings indicate that legumain has a high potential to be a candidate for distinguishing tumors from normal tissues. Although further studies on a larger number of cases are necessary to clarify the clinical application of legumain, the overexpression patterns of legumain in canine tumor tissues are reported, for the first time, in this study.