BACKGROUND: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. METHODS: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. RESULTS: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). CONCLUSION: We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. SIGNIFICANCE: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage.

• Keywords
• BRAF V600E, S100B, ctDNA, ddPCR, melanoma,
• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * genetics   blood   MeSH
• Melanoma * genetics   blood   pathology   diagnosis   surgery   MeSH
• Mutation * MeSH
• Biomarkers, Tumor * blood   genetics   MeSH
• Skin Neoplasms * blood   genetics   pathology   diagnosis   surgery   MeSH
• Predictive Value of Tests MeSH
• Prognosis MeSH
• Proto-Oncogene Proteins B-raf * genetics   blood   MeSH
• S100 Calcium Binding Protein beta Subunit * blood   genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Liquid Biopsy methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• BRAF protein, human MeSH Browser
• Biomarkers, Tumor * MeSH
• Proto-Oncogene Proteins B-raf * MeSH
• S100 Calcium Binding Protein beta Subunit * MeSH
• S100B protein, human MeSH Browser