BETA-3 INTEGRIN EXPRESSION IN MELANOMA PREDICTS SUBSEQUENT METASTASIS

Previous studies have suggested that differential expression and/or ac tivation of integrins facilitates metastatic progression in murine and human melanoma. While recent data show that the integrin alpha v beta 3 is involved in tumor angiogenesis and that tumor growth may be abro gated by (alpha v beta 3 inhibitors in vitro, the clinical significanc e of beta 3 integrin expression in human malignant melanoma is not kno wn. To assess the prognostic value of beta 3 integrin expression, we e xamined primary cutaneous melanomas from 160 patients followed for a m ean of 98 months or until death. We quantified the percentage of tumor area stained with beta 3 integrin Ab CD-61 using an image analyzer. b eta 3 integrin expression was detected in 107/160 primary melanomas (6 9%). beta 3-integrin-positive (beta 3+) tumors were thicker (mean 2.98 +/- 0.3 mm) than beta 3-integrin-negative (beta 3-) melanomas (mean 1 .64 +/- 0.2 mm) (P = 0.002). Patients with beta 3+ melanomas were more likely to relapse (57/107, 53%) and to die from disease (45/107, 42%) than those with beta 3- tumors (6/53, 11%; and 4/53, 8%, respectively ) (P < 0.001). Overall survival was greater for beta 3- than for beta 3+ patients (mean 102 +/- 9 vs 69 +/- 6 months) (P = 0.001). These dat a show that beta 3 integrin expression in primary cutaneous melanoma p redicts subsequent metastatic progression. Further study of beta 3 int egrins in the development of melanoma metastases may yield new therape utic strategies, as well as prognostic information, for the treatment of this cancer. (C) 1996 Academic Press, Inc.