Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 and type 2 in stage I malignant melanoma.

The urokinase-type plasminogen activator (uPA) and its inhibitors type 1 (PAI-1) and type 2 (PAI-2) are considered to have a key role in the process of invasion and metastasis. We investigated the differences in uPA, PAI-1 and PAI-2 concentrations in primary cutaneous melanoma and normal skin and correlations with well-established melanoma prognostic factors. The study was performed on 43 patients (19 men, 24 women; mean age 57 years) with histologically confirmed primary melanomas <1.5 mm thick. The uPA concentrations were determined in 36 pairs of triton extracts, and the PAI-1 and PAI-2 concentrations in 43 pairs of cytosols prepared from the tumour and adjacent normal tissue samples (matched pairs). The uPA, PAI-1 and PAI-2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Significantly higher concentrations of both uPA and PAI-1 were measured in melanomas than in normal surrounding skin (uPA: 1.08 vs 0.48 ng/mg total protein (mgp), p<0.001; PAI-1: 14.07 vs 2.07 ng/mgp, p<0.001). The melanoma uPA, PAI-1 and PAI-2 concentrations correlated significantly (p<0.05) with normal skin (r=0.73, 0.54, 0.38 respectively). The uPA concentrations positively correlated with those of PAI-1 measured in melanomas (r=0.45, p<0.01). PAI-1 values were significantly lower (p<0.001) in the melanomas of Breslow thickness < or =0.75 mm, Clark invasion <II, without microscopic ulceration and without vascular invasion (9.68, 4.74, 11.41, 9.5, respectively) than in the melanomas of Breslow thickness >0.75 mm, Clark invasion of > or =II and < or =III, with microscopic ulceration and vascular invasion (22.25, 17.67, 27.67, 37.77, respectively). Determination of uPA and PAI-1 can provide significant additional prognostic information for melanoma patients.