S100B Protein Detection in Serum Is a Significant Prognostic Factor in Metastatic Melanoma

Abstract

The serum detection of S100B, a new melanoma marker, has shown clinical significance in early studies. The aim of our study of 1,339 serum samples from 412 different melanoma patients and 107 control patients was to prove the prognostic value of serum S100B levels in melanoma patients at different stages of disease and at follow-up (median: 30 months). Using a cutoff level of 0.2 μg/l S100B, 5 of 286 patients (1.7%) with primary tumors (stage I/II), 14/73 (19.2%) patients with locoregional metastasis (stage III) and 57/84 (67.9%) patients with advanced disease (stage IV) were S100B positive (statistically significant differences for stage I/II vs. III, I/II vs. IV, and III vs. IV, p < 0.001). The estimated overall survival time was significantly longer (p < 0.001) for patients with S100B values below 0.2 μg/l compared to patients with elevated S100B levels (≥0.2 μg/l), which was independent of the stage of disease (I–IV). Regarding prognosis, we were furthermore able to distinguish different subgroups among stage III and IV patients using S100B serum levels (p < 0.01). Patients with different cutaneous non-melanoma diseases served as S100B-negative controls. S100B serum evaluations using the Sangtec^®100 IRMA are highly specific and sensitive for the detection of metastatic melanoma. S100B has been shown to be a relevant prognostic factor for survival in a study with a large sample size of melanoma patients including close follow-up evaluations.

Tumor type M2 pyruvate kinase (TuM2‐PK) as a novel plasma tumor marker in melanoma

“…[15][16][17][18] In these patients, S100b is a useful prognostic marker with elevated serum levels of S100b indicating a poor overall survival compared to patients with serum concentrations within normal ranges. 19 In tumor-free patients, e.g., after surgical excision of their primary tumor or lymph node metastases, tumor markers like S100b correlating with the tumor load are of no prognostic use. 19 A variety of different proteins of the peripheral blood, in particular in serum, have been investigated for their potential relevance as tumor markers in melanoma revealing similar characteristics as known from S100b.…”

“…19 In tumor-free patients, e.g., after surgical excision of their primary tumor or lymph node metastases, tumor markers like S100b correlating with the tumor load are of no prognostic use. 19 A variety of different proteins of the peripheral blood, in particular in serum, have been investigated for their potential relevance as tumor markers in melanoma revealing similar characteristics as known from S100b. [20][21][22] However, clinical studies comparing a potential new marker with the well-established marker S100b, or even combining both markers, the new and the familiar one, have been rarely performed up to now.…”

Circulating Serologic and Molecular Biomarkers in Malignant Melanoma

“…These findings were confirmed by several early studies, which reported that the serum level of S100B correlated with clinical stage in patients with malignant melanoma, with the highest levels being seen in disseminated disease. [21][22][23][24][25] In 1995, a study of 126 patients by Guo et al 21 found that serum S100B concentrations were normal in all healthy patients and in those with benign skin lesions and elevated in 1.3%, 8.7%, and 73.9% of patients with stage I/II, III, and IV disease, respectively. Given the low incidence of elevated levels of S100B in serum in early-stage disease, S100B was not found to be useful for screening or early detection.…”

“…22,[24][25][26][27] 24 demonstrated a correlation between serum S100B levels and Breslow thickness, a validated prognostic factor. A combined serum S100B threshold greater than 0.22 μg/L and a Breslow thickness greater than 4 mm had a sensitivity and specificity for the presence of disseminated disease of 91% and 95%, respectively, and may provide a better indication of prognosis at diagnosis.…”

The Roles of S100 Proteins and RAGE in Melanoma

“…Besides these established prognostic markers, the S100 protein family member S100B has emerged in recent years as a new prognostic marker and is now incorporated into the American Joint Committee on Cancer (AJCC) melanoma staging system for stage IV melanoma patients (Balch et al 2009;Chun et al 2008;Gogas et al 2009). High S100B serum concentration correlates with poor survival rate (Hauschild et al 1999). Current studies are also analyzing the prognostic value of S100B in earlier melanoma stages (IIB-III) (Bouwhuis et al 2010).…”