Relevance of MIA and S100 serum tumor markers to monitor BRAF inhibitor therapy in metastatic melanoma patients

• Published in: Clinica chimica acta Vol. 429; pp. 168 - 174
• Main Authors: Sanmamed, Miguel F., Fernández-Landázuri, Sara, Rodríguez, Carmen, Lozano, María D., Echeveste, José I., Pérez Gracia, Jose Luis, Alegre, Estibaliz, Carranza, Omar, Zubiri, Leyre, Martín-Algarra, Salvador, González, Alvaro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2014
• Subjects: Biomarkers, Tumor - blood; BRAF; Extracellular Matrix Proteins - blood; Female; Humans; L-Lactate Dehydrogenase - blood; Male; Melanoma; Melanoma - blood; Melanoma - diagnosis; Melanoma - drug therapy; Melanoma - pathology; MIA; Middle Aged; Neoplasm Metastasis; Neoplasm Proteins - blood; Prognosis; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; S100; S100 Proteins - blood; Skin Neoplasms - blood; Skin Neoplasms - diagnosis; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Therapy; Treatment Outcome; Tumor marker; Tumor marker; Therapy; MIA; Melanoma; iBRAF; S100; BRAF; BRAF inhibitor; serine-threonine protein kinase B-RAF; Melanoma Inhibitory Activity
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2013.11.034

BRAF V600 mutation has been reported in more than 50% of melanoma cases and its presence predicts clinical activity of BRAF inhibitors (iBRAF). We evaluated the role of MIA, S100 and LDH to monitor iBRAF efficiency in advanced melanoma patients presenting BRAF V600 mutations. This was a prospective study of melanoma patients harboring the BRAF V600 mutation and treated with iBRAF within a clinical trial (dabrafenib) or as part of an expanded access program (vemurafenib). MIA, S100 and LDH were analyzed in serum at baseline, and every 4–6weeks during treatment. Eighteen patients with melanoma stages IIIc–IV were enrolled with 88.8% of response rate to iBRAF. Baseline concentrations of all the tumor markers correlated with tumor burden. MIA and S100 concentrations decreased significantly one month after the beginning of treatment and, upon progression, their concentrations increased significantly above the minimum levels previously achieved. MIA levels lower than 9μg/L one month after the beginning of treatment and S100 concentrations lower than 0.1μg/L at the moment of best response were associated with improved progression-free survival. In conclusion, MIA and S100 are useful to monitor response in melanoma patients treated with iBRAF. •Basal MIA and S100 levels correlated with tumor burden using the RECIST 1.1 criteria.•MIA and S100 levels decrease significantly one month after beginning of treatment with iBRAF.•MIA and S100 levels increase significantly during progression.•S100 and MIA levels during treatment were of prognostic value.•Low S100 and MIA levels were associated with better progression-free survival.