Clinical value of combined determination of plasma l-DOPA/tyrosine ratio, S100B, MIA and LDH in melanoma

Abstract

Aim of the study l-DOPA/tyrosine ratio (an index of tyrosinase activity), melanoma antigens S100B and MIA, lactate deshydrogenase (LDH) and their combinations were evaluated for clinical value as tumour markers in melanoma. Methods Blood samples were obtained in 170 melanoma patients (stage I–II: n = 57, III: n = 54, IV: n = 59) at inclusion and in a sub-group of 82 subjects during follow-up for up to 4 years. Laboratory analyses were performed by HPLC ( l-DOPA, l-tyrosine), immunoassays (S100B, MIA) and colourimetry (LDH). Results All markers, except LDH, were elevated in stage IV versus other stages. S100B and MIA highly correlated, especially in stage IV ( r s : 0.849, p < 0.001). The combination of l-DOPA/tyrosine ratio with S100B displayed the highest sensitivity/specificity (73/70%) to confirm stage III–IV or stage IV alone (69/75%) (ROC optimised cut-off). Only the l-DOPA/tyrosine ratio significantly increased (+36% over 5 months, p = 0.001) during progression from stage I–III to higher stages. S100B, MIA and LDH, but not the l-DOPA/tyrosine ratio, responded to progression towards death in stage IV. All markers exhibited a prognostic value in deceased patients ( n = 44); S100B and MIA were the best predictors of survival time by Cox proportional-hazards regression. Conclusion The combination of plasma l-DOPA/tyrosine ratio and S100B appears an attractive approach for the biological follow-up of melanoma patients.