Abstract
PURPOSE: The intercellular adhesion molecule (ICAM)-1 is expressed on many cell types including endothelial cells and different cancer cell entities. Experimental data strongly indicate that ICAM-1 can activate intracellular signalling pathways in cancer cells leading to enhanced cell motility, invasion and metastasis. Yet, little is known about the role of ICAM-1 expression during malignant progression in breast cancer patients. METHODS: We investigated ICAM-1 protein and mRNA expression in two partly overlapping cohorts of breast cancer patients. ICAM-1 protein was detected by Western blot analysis in 104 cases and verified by immunohistochemistry. Additionally, ICAM-1 mRNA microarray data from 169 tumours were analysed. RESULTS: With both methods, high ICAM-1 expression was significantly associated with a poorly differentiated phenotype, a negative estrogen receptor (ER) status and positive lymph node involvement. In addition, there was a significant prognostic impact of ICAM-1 protein overexpression on recurrence-free survival (HR = 2.82, P = 0.023), which was most pronounced in ER-negative tumours. ICAM-1 mRNA overexpression was associated with high urokinase plasminogen activator (uPA) and uPA-inhibitor protein 1 (PAI 1) protein and mRNA levels as well as high Ki67 protein and vascular endothelial growth factor (VEGF) mRNA expression. CONCLUSIONS: In our group of patients, ICAM-1 expression was associated with a more aggressive tumour phenotype. Because of its association with malignant progression, ICAM-1 might represent a new target in the treatment of breast cancer patients.