Expression and Prognostic Value of L1-CAM in Breast Cancer.

Background: The L1 cell adhesion molecule (L1-CAM) has been shown to be involved in cell motility, invasion, chemoresistance and tumor growth in various experimental models, and is associated with impaired prognosis in melanoma, colon and ovarian cancer. However, limited information about its expression in breast cancer is available. Methods: To analyse its role and possible prognostic value in primary breast cancers, L1-CAM mRNA and protein expression using microarray analysis (n=167) and Western Blotting (n=106) was performed. Its cellular distribution was demonstrated by immunohistochemistry. The results were correlated with classical histological data, biologically relevant disease markers and clinical data including disease outcome. Results: L1-CAM mRNA overexpression and protein expression was observed in 14-15% of the carcinomas and its expression was confirmed by immunohistochemical staining. Generally tumour cells at the tumour stroma interface were L1-positive. High L1-CAM expression was associated with nodal involvement, high grading, human epidermal growth receptor 2 (Her-2), plasminogen activator inhibitor 1 (PAI-1) and vascular endothelial growth factor (VEGF) expression and a negative estrogen receptor (ER) status, but not with neuroendocrine markers. High L1-CAM mRNA expression in primary breast cancers was associated with a significantly shorter disease-free (p=0.011) and overall survival (p=0.005). Conclusions Our results indicate that L1-CAM is highly expressed in a relatively agressive subgroup of breast cancers. Given the emerging functional role of L1-CAM in promoting tumor growth and metastasis our results suggest that L1 may have this function in breast cancer as well. Thus, L1-CAM might be a suitable target for specific immunotherapies in selected high-risk breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3044.