Abstract
Purpose: :
About 50% of patients with uveal melanoma develop metastasis independent of the treatment of the primary tumor. We intended to establish a panel of serum and plasma markers recognizing early metastasis in patients with uveal melanoma.
Methods: :
Serum and plasma samples were acquired from 149 patients with uveal melanoma (14 patients with metastatic disease = group M and 135 patients without overt metastasis = group U) and 17 healthy controls (group C). Blood samples were analyzed quantitatively by means of ELISA with respect to GDF-15 (Growth differentiation factor 15), Osteopontin, Melanoma inhibitory activity (MIA), sVCAM (soluble vascular cell adhesion molecule), ICAM-2 (intercellular adhesion molecule 2), TIMP-1 (tissue inhibitor of metalloproteinase 1) and TIMP-2 (tissue inhibitor of metalloproteinase 2).
Results: :
The median GDF-15 level was 1.06 ng/ml (C; SD ± 0.54), 2.53 ng/ml (M; SD ± 23.18) and 1.38 ng/ml (U; SD ± 0.91). The median Osteopontin level was 67.46 ng/ml (C; SD ± 23.4), 123.11 ng/ml (M; SD ± 177.44) and 71.02 ng/ml (U; SD ± 26.7). The median MIA concentration was 6.36 ng/ml (C; SD ± 1.98), 10.04 ng/ml (M; SD ± 12.33) and 6.96 ng/ml (U; SD ± 2.77). The median sVCAM level was 447.14 ng/ml (C; SD ± 137.77), 626.05 ng/ml (M; SD ± 474.98) and 391.32 ng/ml (U; SD ± 194.58). The median concentration of TIMP-1 was 203.19 ng/ml (C; SD ± 22.95), 236.07 ng/ml (M; SD± 138.77) and 208.76 ng/ml (U; SD ± 42.32). The median TIMP-2 level was 93.57 ng/ml (C; SD ± 13.96), 101.81 ng/ml (M; SD ± 39.85) and 97.22 ng/ml (U; SD ± 18.49). The median ICAM-2 concentration was 338.57 ng/ml (C; SD ± 64.79), 326.89 ng/ml (M; SD ± 192.88) and 324.1 ng/ml (U; SD ± 16). There was a significant difference between group C and M (all p's <0.025) and group M and U (all p's<0.03) for all markers, except for ICAM-2. Only GDF-15 showed a significant difference between group C and group U (p<0.002).
Conclusions: :
GDF-15, Osteopontin, MIA, sVCAM, TIMP-1 and TIMP-2 concentrations allow to differentiate between uveal melanoma patients with and without metastasis. The panel can therefore be used for blood monitoring with respect to the development of metastatic disease in uveal melanoma patients.
Keywords: oncology • tumors • melanoma