Upregulation of SLUG expression in canine mammary gland tumors and its prognostic significance

BACKGROUND: SLUG (also known as snai2), which is a transcription factor in epithelial–mesenchymal transition (EMT), plays an important role in tumorigenesis. Several human studies have revealed that SLUG expression downregulates E-cadherin activity to induce metastasis and invasion of tumor cells, and its association with tumor mechanisms is under constant evaluation. In clinical veterinary medicine, one study revealed upregulated SLUG expression in canine oral squamous cell carcinoma. However, the association between canine mammary gland tumors (MGT), the most common neoplasm in intact female dogs, and SLUG has not been investigated yet. Therefore, this study aimed to evaluate the differences in SLUG expression among canine normal mammary gland tissue and MGTs using immunohistochemistry. In addition, its prognostic significance was evaluated by analyzing the correlation with the Ki-67 proliferation index and various clinicopathological features. RESULTS: SLUG expression increased substantially from normal mammary gland tissues to MGTs, especially showing the strongest expression in malignant MGT than in benign MGT. Negative SLUG expression was observed in mostly normal mammary gland tissues, whereas all tissues in malignant MGT showed positive SLUG expression. Furthermore, positive SLUG expression was associated with higher Ki-67 index, larger tumor size (> 3 cm), and metastasis. Kaplan–Meier survival curve analysis revealed that positive SLUG expression was significantly associated with poor overall and disease-free survival. CONCLUSIONS: These results indicate that SLUG is upregulated in canine MGTs and positive SLUG expression is positively correlated with poor prognosis. Thus, SLUG protein can be a novel biomarker and therapeutic target for canine patients with MGT.