Rising levels of serum S100 protein precede other evidence of disease progression in patients with malignant melanoma

Background Several serum markers may be useful in the detection of metastat ic melanoma, but none is in routine clinical use. Objective To assess the validity of S100 protein as a serum marker of melan oma progression. Methods Serum S100 protein levels were measured in 496 serum samples from 2 14 melanoma patients, using the Sangtec luminescence immunoassay. There wer e 75 patients with stage 1 melanoma, 66 initially with stage 2 melanoma, 49 initially with stage 3 melanoma and 24 with stage 4 melanoma. Results Serum S100 protein levels were <0.2 mu g L-1 in 71 of 75 (95%) stag e 1 patients. One patient who had a normal level developed local recurrence . Fifty-eight of 66 (88%) stage 2 patients also had normal serum S100 prote in levels. One with elevated levels progressed to stage 3 melanoma and five with elevated levels progressed to stage 4 disease. The remaining two with elevated serum S100 protein remained well. Thirty-five of 49 (71%) stage 3 patients had normal levels and, of these, two have progressed to stage 4 d isease. Three patients with stage 3 disease had an elevated serum S100 prot ein level on one occasion but remained well. Eleven of 13 patients who deve loped stage 4 melanoma during the study had rising levels of serum S100 pro tein >0.2 mu g L-1 5-23 weeks before detection of melanoma progression by c onventional means. Twenty-two of 24 patients with stage 4 disease throughou t the study had consistently elevated serum S100 protein levels, and the tw o patients with normal levels were clinically disease free after surgery an d chemotherapy. None of 14 control subjects with atypical naevi had elevate d S100 protein levels, and only one of 11 healthy normal controls had an el evated level. Conclusions Thus, rising levels of serum S100 protein are a specific and se nsitive clinically relevant marker of tumour progression in melanoma patien ts, which precedes other evidence of melanoma recurrence.