ASSOCIATION WITH CLINICAL OUTCOME OF EXPRESSION OF VLA-4 IN PRIMARY CUTANEOUS MALIGNANT-MELANOMA AS WELL AS P-SELECTIN AND E-SELECTIN ON INTRATUMORAL VESSELS

Background: The process of tumor growth and metastasis is a complex mu ltistep cascade. The ability of tumor cells to adhere to and detach fr om extracellular matrix and endothelial cells may be crucial in the me tastatic process and may dramatically alter the clinical prognosis and outcome for patients with certain cancers. A number of adhesion molec ules have been detected on human melanoma cells and have been associat ed with various properties in vitro including invasiveness. Recent fin dings from our laboratory have indicated an ordered change in integrin expression during the process of tumor progression. Purpose: This stu dy was designed to identify molecular markers present on human melanom a cells and in intratumoral vessels that have prognostic significance regarding disease-free interval and survival time. Methods: Specimens of primary cutaneous malignant melanoma were obtained from 60 patients who had been followed for at least 36 months, with development of met astases in 29 patients during that period of time, and were analyzed f or their expression of VLA-4, VLA-6, ICAM-1, ELAM-1 (E-selectin), CD62 (P-selectin), and CD44v6 molecules on tumor and endothelial cells by immunostaining. Light microscopy was used to evaluate and categorize t he number of positively stained cells. Statistical analyses were done to determine the relationship of the expression of individual adhesion molecules with time to disease progression (i.e., disease-free interv al) and overall survival time. Results: In each case, positive stainin g for ELAM-1 and CD62 on intratumoral vessels and for VLA-4 on human m elanoma cells was negatively associated with disease-free interval and overall survival time The presence of VLA-6, CD44v6, and ICAM-1 on me lanoma cells was not associated with clinical outcome. Conclusions: Im munohistochemical screening and detection of ELAM-1, CD62, and VLA-4 m ay help to define a subgroup of melanoma patients at risk of developin g metastases.