Soluble HLA‐DR is a potent predictive indicator of disease progression in serum from early‐stage melanoma patients

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Abstract
Despite numerous therapeutic options, the prognosis of malignant melanoma, once metastasized, is still poor. Thus, the search for reliable methods to identify patients with high risk of disease progression as early as possible is of major importance. In our study, we analyzed the predictive value of soluble HLA‐DR (sHLA‐DR) in comparison to S100‐β in serum from 183 melanoma patients of different stages of disease and with or without current therapy using immunosorbent assays. sHLA‐DR serum levels of 121 healthy individuals served as controls. We found significantly (p< 0.0005) reduced sHLA‐DR serum levels in melanoma patients (0.70 ± 0.08 SEM μg/ml) compared to controls (1.49 ± 0.10 SEM μg/ml). Reduced sHLA‐DR and increased S100‐β levels were associated with advanced disease stages and tumor load. S100‐β was increased under cytostatic therapy (p< 0.0005), whereas sHLA‐DR was not influenced by therapy modalities. Univariate analysis showed an association of sHLA‐DR < 0.3 μg/ml and S100‐β > 0.12 μg/l with poor overall (p= 0.021 andp= 0.0009) and progression‐free survival (p< 0.0005 andp= 0.0025). Multivariate analysis revealed disease stage (p= 0.0093) and tumor burden (p< 0.0005) as independent predictive factors for overall survival, and sHLA‐DR (p= 0.0007) and tumor burden (p= 0.0015) for progression‐free survival. In contrast to S100‐β, sHLA‐DR serum concentrations < 0.3 μg/ml were strongly associated (p= 0.0001) with poor progression‐free survival in a subgroup of 60 nonmetastasized patients. In conclusion, our results suggest sHLA‐DR as a potent prognostic serum marker in melanoma patients superior to S100‐β in helping to identify early‐stage patients at high risk of disease progression.