The Dynamics of Serum Tumor Markers in Predicting Metastatic Uveal Melanoma (Part 1)

Aim: To examine the kinetics of the tumor marker levels: osteopontin (OPN), S-100 beta, melanoma inhibitory activity (MIA) and tissue polypeptide-specific antigen (TPS), and to evaluate their potential for predicting earlier liver metastasis in patients with uveal melanoma (UM). Patients and Methods: Forty-three UM patients who remained disease-free (DF) for at least 10 years, 32 patients with metastatic UM and 53 healthy controls were enrolled. Median and mean levels of the tumor markers OPN, S-100 beta, MIA and TPS at the time periods of 0-6, 6-12, 12-18, 18-24 and >24 months prior to confirmation of metastasis by liver ultrasound, CT scan and biopsy, served in a box and whiskers analysis and were compared by Students t-test. Trends of changes in marker levels of DF and metastatic UM groups were calculated and compared by ANOVA. Results: The lead-time for predicting metastasis was: 12-18 months both for OPN (p=0.005) and MIA (p=0.37), for S-100 beta 1824 months first increase (p=0.5) followed by a second one 0-6 months (p=0.01) and for TPS 18-24 months (p=0.1). The gradient of the trendlines for the metastatic group was significantly steeper for MIA (p=0.02) and S-100 beta (p=0.018) than for the DF group and not statistically significant for OPN (p=0.168). For TPS, the trendline was negative. The overall increase in the levels of OPN and S-100 beta was significant, while for TPS and MIA, it was not. Conclusion: Significant increases in OPN and S-100 beta levels were demonstrated by a major lead time. Trendlines of the metastasis group were steeper than of the DF group predicting liver metastasis. The routine use of those markers in the follow up of UM patients, can enable earlier diagnosis of liver metastasis and effective therapeutic intervention, with an impact on survival.