The Clinical Significance Of L1-CAM Expression In Breast Cancer

Objective:Cancer invasion is a cell and tissue-driven process.Cancer invasion is initiated and maintained by signaling pathways that control cell-matrixand cell-cell adhesion, followed by cell migration into the adjacenttissue. Invasive micropapillary carcinoma (IMPC) of the breast is a newly recognzed subtype of breast cancer characterized by a high propensity for lymph node metastasis. The study aims to investigate the expression of L1cell adhesion molecules (L1-CAM) in IMPC and to analyze its clinical significance; to investigate the expression and clinical significance of L1-CAM and β-cat in breast invasive ductal carcinoma.Methods:L1-CAM expression was analyzed in97IMPCcases (95cases of invasive ductal carcinoma-not other wises pecified, IDC-NOS,as control group); two hundred and three surgically speciments of IDC-NOS were examined via immunohistochemistry using monoclogical against L1-CAM and β-cat.The correlations between the expression of the proteins and clinicopathologic characteristics, which include the prognosis patients was determined.Results:1. The L1-CAM expression predominantly in the cell-cell interface of the cell clusters of IMPC and L1-CAM staining on the stroma vascular endothelial cells inIMPC were higher than IDC-NOS (p<0.05).2. The rate of L1-CAM expression in IMPC (50.5%) was significantly higher than that of IDC-NOS (18.9%), it was also associated with histological grade, Vessels invasion, lymph node metastasis, L1-CAM vessels and protein p53expression (p<0.05), negatively associated with ER and PR (p<0.05).3. Univariate analysis indicated that expression of Ll-CAM was a risk factor predicting IMPC patient survival (p<0.05). Multivariate analyses done by Cox proportional hazards model showed that high expression of L1-CAM was an independent risk factor for IMPC patient’s death.4. L1-CAM was not expressed in normal breast duct epithelium but was aberrantly expressed inl6.3%of IDC-NOS tumors. In most cases (32/33), high expression of L1CAM was localized at the invasive front of the tumor tissue. Abnormal expression of β-cat was in61%of IDC-NOS tumors.5. The expressions of the two proteins were not associated with patient age or gender in IDC-NOS, but with histological grade and lymph node metastasis. L1-CAM expression was also correlated with extranodal and distant metastasis extension..There was a positive correlation between L1CAM and β-cat (p<0.05).6. Survival analysis showed that expression of L1-CAM and abnormal expression of β-cat were statistically significantly related to poor survival. Multivariate analysis revealed that LI-CAM expression was an independent prognostic factor predicting overall survival of IDC-NOS patients.Conclusions:1. The expression of L1-CAM in IMPC was significantly higher than in IDC-NOS group, suggesting that activation of the L1-CAM gene may play a role in the malignant progression of breast cancer, which may be the key factors that prompted IMPC lymph node metastasis.2. This study suggests that L1-CAM expression may play an important role in collective cell growth and was significantly associated with tumor invasion and metastasis.Studies suggest that L1-CAM, E-CD co-expressed in the IMPC group, jointly coordinated collective cell growth and lymph node metastasis by increasing the ability of cancer cell adhesion in the cell clusters of IMPC groups.3. L1-CAM located in the lymphatic endothelium of tumor stroma may be a key factor of IMPC highly addicted to lymphoid (high lymphatic invasion, high lymph node metastasis).4. L1-CAM could be considered as biomarkers of prognosis and as a new target for IMPC therapy.5. The positive correlation between L1-CAM and β-cat ectopic expression indicates that they may have mutual regulation in the IDC-NOS, both of which may be provided by EMT in breast cancer invasion.6. L1-CAM expression may play an important role in the IDC-NOS invasion and metastasis and was a new molecular markers new IDC-NOS clinical prognosis.