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 multistep cascade. The ability of tumor cells to adhere to and detach from extracellular matrix and endothelial cells may be crucial in the metastatic process and may dramatically alter the clinical prognosis and outcome for patients with certain cancers. A number of adhesion molecules have been detected on human melanoma cells and have been associated with various properties in vitro including invasiveness. Recent findings from our laboratory have indicated an ordered change in integrin expression during the process of tumor progression.


OBJECTIVE
This study was designed to identify molecular markers present on human melanoma 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 metastases in 29 patients during that period of time, and were analyzed for 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 the 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 interval) and overall survival time.


RESULTS
In each case, positive staining for ELAM-1 and CD62 on intratumoral vessels and for VLA-4 on human melanoma cells was negatively associated with disease-free interval (P < .01) and overall survival time (P < .01). The presence of VLA-6, CD44v6, and ICAM-1 on melanoma cells was not associated with clinical outcome.


CONCLUSIONS
Immunohistochemical screening and detection of ELAM-1, CD62, and VLA-4 may help to define a subgroup of melanoma patients at risk of developing metastases.
Schadendorf
D
D
Department of Dermatology, University Hospital Rudolf Virchow, Freie Universität Berlin, Federal Republic of Germany.
Heidel
J
J
Gawlik
C
C
Suter
L
L
Czarnetzki
B M
BM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015815:Cell Adhesion Molecules / Q000032:analysis*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000737:chemistry*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000737:chemistry* / Q000556:secondary; D008875:Middle Aged; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011237:Predictive Value of Tests; D016029:Receptors, Very Late Antigen / Q000032:analysis*; D012878:Skin Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D016029:Receptors, Very Late Antigen