Serum S100 – A Marker for Disease Monitoring in Metastatic Melanoma

Henze, Günter; Dummer, Reinhard; Joller‐Jemelka, H. I.; Böni, R.; Burg, Günter

doi:10.1159/000246103

Cited by 117 publications

(99 citation statements)

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“…Despite other data supporting the value of serum S-100B as a clinical marker for monitoring therapy response of metastatic melanoma during systemic therapies a clear drawback of this tumormarker is the fact that it has a false negative rate in one third of patients with metastases (7,28,29). In the present study 36% patients failed to show elevated S-100B values despite the presence of proven distant metastases.…”

Section: Discussioncontrasting

confidence: 75%

Chemotherapy response assessment in stage IV melanoma patients—comparison of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B

Strobel

Dummer

Steinert

et al. 2008

Eur J Nucl Med Mol Imaging

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PURPOSE: This study aims to compare the use of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B in chemotherapy response assessment of stage IV melanoma patients. METHODS: In 25 patients with stage IV melanoma, FDG-PET/CT and S-100B after 2-3 months (three cycles) of chemotherapy was compared with baseline PET/CT and baseline S-100B. Retrospectively, the response was correlated with the outcome. In patients with clinical suspicion for brain metastases, MRI or CCT was performed. RESULTS: There was agreement between FDG-PET/CT and CT regarding response to chemotherapy in all patients. There was a clear trend to a longer OS of PET/CT responders (n = 10) compared with PET/CT non-responders (n = 15; p = 0.072) with remarkably better 1-year OS of 80% compared to 40% (p = 0.048). There was a significant longer PFS of PET/CT responders compared with PET/CT non-responders (p = 0.002). S-100B was normal at baseline in eight of 22 patients where it was available. Chemotherapy response assessment with S-100B failed to show correlation with OS or PFS. Eleven patients developed brain metastases during treatment, first detected by PET/CT in two and by MRI or CCT in nine of 11 patients. Appearance of brain metastases was associated with a poor survival. CONCLUSIONS: 18F-FDG-PET/CT and CT alone are equally suitable for chemotherapy response assessment in melanoma patients and clearly superior to S-100B. PET/CT responders have better early survival, but this is shortlived due to late therapy failure-often with brain recurrence. Additional brain MRI for therapy response assessment in such high-risk patients is mandatory to detect brain metastases missed by PET/CT. Chemotherapy Response Assessment in MethodsIn 25 patients with stage IV melanoma FDG-PET/CT and S-100B after 2-3 months (3 cycles) of chemotherapy was compared with baseline PET/CT and baseline S-100B.Retrospectively, the response was correlated with the outcome. In patients with clinical suspicion for brain metastases MRI or CCT was performed. ResultsThere was agreement between FDG-PET/CT and CT regarding response to chemotherapy in all patients. There was a clear trend to a longer OS of PET/CTresponders (n=10) compared with PET/CT non-responders (n=15) (p=.072) with remarkably better 1-year OS of 80% compared to 40% (p=.048). There was a significant longer PFS of PET/CT-responders compared with PET/CT nonresponders (p=.002). S-100B was normal at baseline in 8 of 22 patients where it was available. Chemotherapy response assessment with S -100B failed to show correlation with OS or PFS. 11 patients developed brain metastases during treatment, first detected by PET/CT in 2 and by MRI or CCT in 9 of 11 patients.Appearance of brain metastases was associated with a poor survival.

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Section: Discussioncontrasting

confidence: 75%

Chemotherapy response assessment in stage IV melanoma patients—comparison of 18F-FDG-PET/CT, CT, brain MRI, and tumormarker S-100B

Strobel

Dummer

Steinert

et al. 2008

Eur J Nucl Med Mol Imaging

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“…Previous studies with the more insensitive immunoradiometric assay (IRMA) using pretreatment serum samples of patients with cutaneous malignant melanoma reported a relation between stage of the disease and the median concentration of S-1OOB protein, although an adequate assessment of the sensitivity of the S-1OOB was not possible (Von Schoultz et al, 1996;Henze et al, 1997). Bei Guo et al (1995) found positive S-1OOB values in 13% of stage IIIB patients, contrary to 33% in this study.…”

Section: Discussionmentioning

confidence: 99%

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

Bonfrèr

Korse²,

Nieweg³

et al. 1998

Br J Cancer

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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...

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“…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.…”

Section: Lactate Dehydrogenasementioning

confidence: 99%