Expression and serum levels of MMP-2 and MMP-9 during human melanoma progression

Matrix metalloproteinases (MMP)-2 and -9 have been implicated in malignant tumour progression, partly because they degrade collagen type IV, a major component of basement membranes. Biopsy specimens from 56 patients with primary melanoma and 7 with cutaneous or nodal metastases were studied by immunohistochemistry. Of 39 patients with estimated good prognosis, 70.5% of melanomas were negative for MMP-2, compared with only 47% of 17 melanomas in patients who developed metastasis during the 3-year follow-up. All skin and nodal metastases were negative for MMP-2 and positive for MMP-9. Of 14 thick melanomas, 9 were mostly positive for MMP-2 expression, suggesting a possible association with the invasiveness of the melanoma. MMP-2 and MMP-9 plasma levels were analysed in another 29 patients with melanoma (10 stage I and II, 9 stage III, and 10 stage IV) and in 10 healthy controls. No difference in MMP-9 plasma levels was found among the groups. Higher MMP-2 concentrations were observed in patients with metastatic disease (stage IV) than in those with primary melanoma (stage I) or in controls. Serial levels in two patients who passed from stage I to stage III or IV showed no significant difference in MMP-2 or -9 values. We conclude that MMP-2 expression might be associated with progression of the melanoma. Circulating MMP-2 and -9 levels have shown low sensitivity and specificity, so they do not seem to be good tumour markers in patients with melanoma.