The luminescence immunoassay S-100: a sensitive test to measure circulating S-100B: its prognostic value in malignant melanoma

Abstract

Summary In this study we measured S-1i OB using a recently developed luminometric immunoassay with a detection limit of 0.02 gg l-1. By measuring serum S-1O0B concentrations in 58 apparently healthy individuals a reference value of 0.16,ug 1-1 was found. To assess the sensitivity of the assay we measured levels of S-100B protein in the serum of 251 patients with cutaneous malignant melanoma before the start of treatment. Only one of 179 patients with limited disease had a serum concentration higher than the reference value, whereas elevated levels were seen in 79% of patients with metastasized disease. In the latter group the NSE serum concentration was elevated in 42%. Using a receiver operating characteristic (ROC) curve it is shown that S-1 00B is a significantly better parameter than neuron-specific enolase (NSE) for distinguishing patients with limited disease from those with extensive melanoma. Pretreatment S-100B values were highly predictive for the period of survival. Patients with limited disease have increased risk for early death with increasing levels of S-100B protein. Within the group of patients with positive lymph nodes and/or with distant metastases, elevated S-100B levels strongly identified high-risk patients. Our study indicates that the measurement of S-1 QOB as a tumour marker in the management of patients with cutaneous malignant melanoma has clinical significance.Keywords: malignant melanoma; serum S-10OB; luminometric assay; sensitivity; survival The use of tumour markers in melanoma was initially limited to the measurement of neuron-specific enolase (NSE), which is the y isoenzyme of the enolase enzyme (Wibe et al, 1990). Results have been disappointing and this assay has not gained a place in the monitoring of patients treated for malignant melanoma. The demonstration that the S-100 protein is expressed in cultured melanoma cells (Gaynor et al, 1980) opened the way for investigations into the presence of the S-100 protein in a variety of tissues. As the protein was initially extracted from brain tissue it was not surprising that the molecule was detected in other tissue apart from melanocytic cells (Cochran et al, 1993). The S-100 protein family belongs to the EFhand proteins, and to date 17 different proteins have been assigned to this family (Schafer and Heizmann, 1996). S-1OOB is formed by homodimers consisting of two P subunits or heterodimers of x and f subunits with equal molecular mass of 10.5 Da. The isoform a,B is found in melanocytes and the DP is found in high concentrations in glial cells and Schwann cells. S-IOOAI (aaox) is found in striated muscle, heart and kidney (Baudier et al, 1986).The function of S-100 is not known exactly but its biochemical properties strongly suggest that it activates cell processes along the Ca2+ signal-transduction pathway (Schafer and Heizmann, 1996). By using monoclonal antibodies against the different isoforms a specific test was developed. Measurement of the S-1 OOB protein in serum has been possible for several years but the assessment of...

The prognostic value of serum S100B in patients with cutaneous melanoma: A meta‐analysis

“…In particular, the prognostic role of S100B consistently retained its significance when series analyzing survival data with the multivariate Cox model were included, which suggests that S100B adds prognostic information to the traditional prognostic factors, such as TNM stage 21,24,29,32,34,37 and LDH. 23,26,30,33 Nevertheless, our findings also hint some considerations that suggest caution in interpreting this favorable outcome and might pave the way to design more informative studies.…”

“…[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]48 In 2 cases, 26,29 the Authors reported survival analysis separately for 2 subpopulations that differed by TNM stage: since these subpopulations were completely independent, we considered them separately (Table I).…”

“…[13][14][15] The prognostic potential of S100B serum levels is supported by many reports in the literature. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Nevertheless, some investigators found no association between S100B detection and patients' survival 26,29 ; moreover, others reported that S100B has a prognostic value at univariate but not multivariate survival analysis, 38 which would rule out the value of this biomarker as a prognostic factor independent of the already established prognostic power of the TNM staging system.…”

Detection of Melanoma Relapse: First Comparative Analysis on Imaging Techniques versus S100 Protein

“…It is expressed in neural cells, melanocytic cells, epidermal Langerhans cells, Merkel cells as well as chondrocytes. It is known that serum levels are elevated in patients with disseminated melanoma [2,3,4,5] and that the S100 level is useful in monitoring the response to chemotherapy in stage IV disease [6, 7]. …”

Serum Protein S-100 Predicts Clinical Outcome in Patients with Melanoma Treated with Adjuvant Interferon – Comparison with Tyrosinase RT-PCR

“…S-100β protein, either in homo- or heterodimeric form, is found immunohistochemically in melanocytes and melanoma cells, as well as in cells derived from the neural crest, monocytes, macrophages, and interdigitating reticulum cells [6,7,8,9]. Different groups have found a correlation between the serum levels of S-100 in melanoma patients with clinical stage, prognosis [10,11,12,13,14,15,16,17,] and response to treatment in patients with metastatic melanoma [18,19,20,21,22]. We hypothesized that high levels of S-100 in patients with resected melanoma may indicate the presence of microscopic disease, while increasing levels may be a marker of disease progression, despite the use of interferon therapy.…”