Prospective monitoring of adjuvant treatment in high-risk melanoma patients: lactate dehydrogenase and protein S-100B as indicators of relapse

Abstract

At present there is no international consensus on laboratory testing during the follow-up of melanoma patients. We carried out a prospective monitoring study on the usefulness of lactate dehydrogenase (LDH) and protein S-100B assessment in high-risk melanoma patients. Ninety-seven patients treated within prospective randomized trials on the adjuvant treatment of melanoma received quarterly clinical visits and blood examinations. During the median observation period of 30 months disease progression was observed in 52 of 97 patients (53.1%). The clinical course of melanoma was correlated to elevated LDH and S-100B serum concentrations. The comparative analysis revealed that (i) neither LDH nor S-100B were indicators of in-transit metastases, (ii) clinically apparent lymph nodes were rarely detected because of elevated S-100B (29.4%) or LDH (11.8%) only, and (iii) the S-100B assessment was superior to LDH in the identification of early distant metastasis (53.8 vs. 23.1%; P=0.008). The rate of false-positive (elevated) LDH-serum levels and S-100B-serum levels in clinically disease-free melanoma patients did not differ significantly (S-100B 1.9% vs. LDH 1.6%). Our data indicate that only protein S-100B might be used as a highly specific and relatively sensitive marker of early distant metastasis. Both markers, LDH and S-100B, are not able to identify loco-regional metastases with a low tumor load in high-risk melanoma patients.

Increased level of circulating U2 small nuclear RNA fragments indicates metastasis in melanoma patients

“…In distant metastasis, for instance, sensitivity (69.6%-76.9%) exceeded that of S100B (55% in AJCC stage IV; 53.8% in high-risk patients upon relapse) and LDH (28% in stage IV; 23.1% upon relapse) [6,17]. At the same time, the rate of false-positive elevated RNU2-1f levels remained excellent in the range of 0%-12.8%, documenting the clinical potential of RNU2-1f as a biomarker for melanoma metastasis.…”

“…The circulating levels of all three biomarkers correlate with tumor burden and appear to be useful, to a certain extent, in monitoring therapy response in relapsed melanoma patients [5]. Whereas increased serum S100B level specifically identifies distant and, to a lesser extent, regional metastasis [6], thus outperforming imaging techniques [7], sensitivity is rather limited, with only approximately half of the distant recurrences being detected. Novel, complementary serum biomarkers are needed therefore to improve early detection and clinical management of advanced melanoma.…”

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

“…In-transit metastases, however, did not lead to increased S100B levels, as shown in an analysis by Egberts et al [621]. In a comparative study, S100B was markedly superior to lactate dehydrogenase (LDH) and alkaline phosphatase (AP) [120].…”

Prognostic and predictive value of YKL-40 in stage IIB-III melanoma

“…The value of monitoring serum YKL-40 during treatment and follow-up in patients with stage IIB and III melanoma needs confirmation in other large prospective studies, and preferably in combination with analysis of lactate dehydrogenase, S100-B protein, and melanomainhibitory activity [36,37].…”