Clinical Significance of Serum Levels of E-Selectin, Intercellular Adhesion Molecule-1, and Vascular Cell Adhesion Molecule-1 in Gastric Cancer Patients Dimitrios Alexiou, M.D., Anastasios J. Karayiannakis, M.Sc., M.D., Konstantinos N. Syrigos, M.D., Ph.D., Andrew Zbar, M.D., Elefteria Sekara, B.Sc., Panagiotis Michail, M.D., Theophilos Rosenberg, M.D., and Theodoros Diamantis, M.D. First Department of Surgery, University of Athens, Medical School, Athens, Greece; Second Department of Surgery, Democritus University of Thrace, Medical School, Alexandroupolis, Greece; Third Department of Medicine, University of Athens, Medical School, Athens, Greece; and Professorial Department of Surgery, University of West Indies, Queen Elizabeth Hospital, Barbados OBJECTIVES: This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. METHODS: The serum concentrations of the adhesion mol- ecules E-selectin, intercellular adhesion molecule-1 (ICAM- 1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. RESULTS: Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selec- tin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly af- ter radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. CONCLUSIONS: These findings suggest that serum concen- trations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful. (Am J Gastroenterol 2003;98:478 – 485. © 2003 by Am. Coll. of Gastroenterology) INTRODUCTION Metastatic spread of cancer cells is a key event in tumor progression and in determining the prognosis of patients with malignant disease. Malignant cells detached from the primary tumor must penetrate into blood or lymph vessels, survive in the circulation, and then arrest in the capillary endothelium of distant organs, extravasate, and grow as secondary lesions (1). Therefore, adhesion interactions be- tween endothelial and cancer cells seem to be crucial for the successful development of metastasis. These interactions are modulated by specific cell surface receptors including the selectins, the integrins, and the immunoglobulin like family of cell adhesion molecules (2). It is now increasingly apparent that certain members of these families of cell adhesion molecules are involved in tumor progression. E-selectin (also known as endothelial leukocyte adhesion molecule–1) is expressed on activated endothelial cells and may bind cells expressing specific carbohydrate ligands containing sialyl-Lewis residues (3). Selectins mediate binding of leukocytes to the microvascu- lar endothelium, and experimental studies have suggested that the efficiency of the E-selectin–mediated binding of certain cancer cell lines to endothelial cells correlates with their metastatic potential (4, 5). Intercellular adhesion mol- ecule–1 (ICAM-1) and vascular cell adhesion molecule–1 (VCAM-1) are both members of the immunoglobulin su- perfamily of adhesion molecules. ICAM-1 is constitutively expressed by endothelial cells and by some leukocytes, and it serves as a ligand for the leukocyte  2 integrin receptors LFA-1 and Mac-1. VCAM-1 is found mainly on activated endothelial cells and provides a ligand for the  4  1 integrin THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 98, No. 2, 2003 © 2003 by Am. Coll. of Gastroenterology ISSN 0002-9270/03/$30.00 Published by Elsevier Science Inc. doi:10.1016/S0002-9270(02)05927-0