Study on the skip metastasis of axillary lymph nodes in breast cancer and their relation with Gli1 expression

The skip metastasis (SM) of axillary lymph nodes (ALN) in breast cancer is an important phenomenon which is crucial to determine the correct choice of surgical resection. The mechanism of SM of ALN is unclear. Gli1 protein is a core epithelial-to-mesenchymal transition (EMT) regulatory factor that plays essential roles in both development and disease processes and has been associated with metastasis in carcinomas. The aim of this study was to investigate the clinicopathological characteristics of SM and evaluate the significance of Gli1 expression in breast cancer patients with metastasis of ALN. Clinicopathological data from 1,037 female breast cancer patients who underwent radical mastectomy were retrospectively reviewed. In this study, an SM was defined as level I absence but level II and/or level III involvement. The expression of Gli1 was evaluated by immunohistochemistry in 102 non-SM cases with positive nodes and 33 SM cases. In univariate analysis, we found that pN category, TNM stage, intrinsic subtypes and Gli1 expression was significant risk factor of SM. Further logistic regression analysis revealed that luminal A cases had a lower risk of SM relative to luminal B 1 (HER2 negative) cases. Further multivariate analysis revealed that Gli1 expression and numbers of positive lymph nodes were the independent factors which associated with SM. Collectively, Breast cancer with SM of ALN associated with the intrinsic subtype of the luminal B1. Gli1 expression related with the procession of breast cancer with SM, which can be used as a predictor of SM of ALN in breast cancer.