Previous studies have suggested that differential expression and/or activation of integrins facilitates metastatic progression in murine and human melanoma. While recent data show that the integrin αvβ3 is involved in tumor angiogenesis and that tumor growth may be abrogated by αvβ3 inhibitors in vitro, the clinical significance of β3 integrin expression in human malignant melanoma is not known. To assess the prognostic value of β3 integrin expression, we examined primary cutaneous melanomas from 160 patients followed for a mean of 98 months or until death. We quantified the percentage of tumor area stained with β3 integrin Ab CD-61 using an image analyzer. β3 integrin expression was detected in 107/160 primary melanomas (69%). β3-integrin-positive (β3+) tumors were thicker (mean 2.98 ± 0.3 mm) than β3-integrin-negative (β3-) melanomas (mean 1.64 ± 0.2 mm) (P = 0.002). Patients with β3+ melanomas were more likely to relapse (57/107, 53%) and to die from disease (45/107, 42%) than those with β3- tumors (6/53, 11%; and 4/53, 8%, respectively) (P < 0.001). Overall survival was greater for β3- than for β3+ patients (mean 102 ± 9 vs 69 ± 6 months) (P = 0.001). These data show that β3 integrin expression in primary cutaneous melanoma predicts subsequent metastatic progression. Further study of β3 integrins in the development of melanoma metastases may yield new therapeutic strategies, as well as prognostic information, for the treatment of this cancer.
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