High expression levels of collagenase‐1 and stromelysin‐1 correlate with shorter disease‐free survival in human metastatic melanoma

Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor‐induced angiogenesis. We studied the expression of collagenase‐1 (MMP‐1), stromelysin‐1 (MMP‐3) and collagenase‐3 (MMP‐13) in 70 melanoma metastases obtained from 56 patients treated with combined chemoimmunotherapy. The patients were divided into 2 groups using a cut‐off point of 0% for MMP‐1 expression and 20% for MMP‐3 expression. We found that patients with MMP‐1 positive metastases (n = 38) had significantly shorter disease‐free survival compared to patients with MMP‐1 negative metastases (n = 18) (median 11.2 vs. 17.0 months, p = 0.0383). The disease‐free survival of patients with high levels of MMP‐3 expression in their metastases (≥20% positive tumor cells, n = 14) was also significantly shorter compared to patients with lower levels of expression (n = 42) (median 5.1 vs. 14.0 months, p = 0.0294). The expression of MMP‐13 did not correlate to survival parameters. We also found that the presence of melanin, a pigment produced by melanocytes, correlated with high expression levels of MMP‐1 (p = 0.0002), MMP‐3 (p < 0.0001) and MMP‐13 (p = 0.0009). The high expression levels of MMP‐13 were also associated with the presence of visceral metastases (p = 0.0284). Our findings suggest that MMP‐1 and ‐3 may have a special role in melanoma metastasis formation and thus they could be used to measure the biological activity of the disease. © 2001 Wiley‐Liss, Inc.