Heterogenous S-100B Protein Expression Patterns in Malignant Melanoma and Association with Serum Protein Levels

Abstract

Objective: Serum S-100B is a reliable tumor marker of malignant melanoma, but efficient use is restricted to patients with metastatic disease. Therefore, the aim of our study was to assess serum S-100B levels at different stages of malignant melanoma and to compare these levels with the expression of the S-100B phenotype in primary tumors and lymph node metastases. Methods: Fifty-nine patients were included in this study; serum S-100B protein was measured using an immunoluminometric assay while the expression pattern in the primary tumor was determined by immunohistochemistry using an anti-S-100B monoclonal antibody. Results: Serum S-100B concentrations were significantly elevated in stage III (p = 0.01) patients, with normal levels in stage I–II. The most frequent S-100B protein expression pattern of the melanoma tissue was found to be diffuse staining observed in around half of the cases (52.5%) followed by heterogeneous (30.5%) and focal patterns (17%), being independent of the stage as well as the lymph node involvement. In stage I–II patients, the various staining patterns did not correlate with the serum concentration of the S-100B protein, while in stage III patients with heterogenous or diffuse S-100B staining patterns in tumor tissue, the serum marker concentration was significantly higher (p < 0.05) than in patients with focal staining. Furthermore, S-100B staining of the melanoma tissue also differed (low/negative, medium and strong staining), and serum marker concentrations corresponded to the pattern of the staining intensity. In stage I–II, only strong staining was associated with elevated serum S-100B concentrations while in stage III medium and strong staining was found to be associated with significantly higher serum marker concentrations compared to patients with tumors with low/negative staining (p < 0.05). Conclusions: In malignant melanoma characterized by focal and/or low S-100B staining in the tumor tissue determined by immunohistochemistry, S-100B monitoring in the serum may not suffice to detect disease progression.

Role of serum S100B and PET-CT in follow-up of patients with cutaneous melanoma

“…Authors report that between 41 to 68% of patients with stage III disease do not have an increased serum marker [11,13-15]. In our study 50.0% of patients with metastases limited to the lymph nodes and 42.9% of patients with distant metastases did not have the increased level of serum marker.…”

S100B Protein in Clinical Diagnostics: Assay Specificity

“…Finally, S100B was increased in the blood of patients with malignant melanoma; melanocytes are known to express high amounts of this proteins (13)(14)(15). S100B concentrations in body fluids are usually determined by commercially available immunoassays such as the Can Ag S100 EIA (Can Ag Diagnostics AB, Gothenburg, Sweden), the ELISA NEXUS DX TM S100 (Syn X Pharma Inc., York, U.K.), or the widely used two-site immunoassays (Sangtec ® 100 IRMA, Liaison ® Sangtec 100, Sangtec 100 ELISA) from DiaSorin AB (Bromma, Sweden).…”

Lack of Elevation of Serum S100B in Patients with Metastatic Melanoma as a Predictor of Outcome After Induction with an Autologous Vaccine of Proliferating Tumor Cells and Dendritic Cells

“…7,8 CONCLUSIONS Not all melanomas express S100, but there is some degree of correlation between S100 expression in melanoma tissues and S100B serum levels in patients who have metastatic disease. 25 Immunohistochemical expression of S100 proteins can be characterized as diffuse in about half, focal in one quarter, and a mix of focal and diffuse in about one quarter of patients. It appears that S100B is more likely to be present in association with a diffuse expression of S100.…”

“…It appears that S100B is more likely to be present in association with a diffuse expression of S100. 25 It is possible that the lack or low expression of S100 proteins is associated with a more favorable prognosis. When patients have no measurable disease, and low S100B levels, it is unclear at that time whether it is because they have no detectable metastatic melanoma lesions or because they have subclinical melanoma that does not express S100B.…”