Signaling pathway-related genes identified in EEA with LN metastasis compared to the results of the LVSI-LN- group without metastasis were as follows: genes relating to hypoxia (ERBB2, HK1, PIK3CA), metabolic stress (EZH2, CCNE1, AQP9, ERBB2, HK1, HRAS, H2AFX, HMGA1, ATM, PIK3CA, UBE2C), epigenetic regulation (EZH2, H2AFX, HMGA1), and matrix remodeling and metastasis (COMP, TGFB2, ITGA6, RELN, and NCAM1) (P<0.01) (Figure 4B). This evidence concerns the gene RELN and lobular neoplasia.