Salgado, C.M. (Claudia M.)

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    Alpelisib decreases nevocytes of congenital melanocytic nevi
    (Elsevier, 2023) López-Gutiérrez, J.C. (Juan Carlos); Tomás-Velázquez, A. (Alejandra); Reyes-Múgica, M. (Miguel); Salgado, C.M. (Claudia M.); Andrea, C.E. (Carlos Eduardo) de; Redondo-Bellón, P. (Pedro)
    Background: Multiple, large or giant congenital melanocytic nevi (CMN) are uncommon and affected patients can show progressive growth and thickening, associate neurocutaneous melanocytosis or develop melanoma. Current treatment modalities are mostly complex surgeries that frequently do not solve the disease and its risks completely. Thus, investigation on new treatment options for CMN and its complications must continue. MAPK pathway inhibitors are being investigated, also targeting PI3K-AKT. Omipalisib (PI3K inhibitor, with no indications approved yet) has been studied for CMN in vitro and in mice with promising results. However, alpelisib, a PI3K inhibitor approved with an adequate safety profile for patients with severe manifestations of PROS (PIK3CA-Related Overgrowth Spectrum), had not yet been tested for CMN. Objective: To evaluate the effect of alpelisib in nevocytes of congenital melanocytic nevi. Methods: Nevomelanocytic tissue samples of 10 patients were collected prospectively and, following a previously reported preclinical ex vivo model, explants were placed in organotypic culture for 5 days, with or without alpelisib. Consecutively, tissue sections were stained and using scanned images with Qupath and ImageJ softwares, representative regions from the dermis were analysed (using Wilcoxon test and Spearman's correlation). Results: When comparing alpelisib-treated explants with respect to control explants, we found a decrease in cell density (p = 0.0273), in density of SOX10+ -cells (p = 0.0391) and also in the % of S-100+ area (p = 0.0078), in alpelisib samples. The three markers showed a positive correlation (p < 0.05). Conclusions: This study provides first-time evidence that alpelisib induces nevocyte reduction in CMN from patient-derived explants, probably inducted by autophagy. Alpelisib is an approved drug with an adequate safety profile used in another mosaicism affecting PI3K (PROS). Further studies are needed to evaluate its efficacy in treating CMN and potentially, their complications, either with local or systemic administration, alone or in combination.
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    Serum levels of S-100 protein are directly proportional to the size, number, thickness and degree of cellularity of congenital melanocytic nevi
    (Elsevier, 2023) López-Gutiérrez, J.C. (Juan Carlos); Tomás-Velázquez, A. (Alejandra); Andrés, E.M. (Eva M.); Reyes, M. (Miguel); Salgado, C.M. (Claudia M.); Ceballos-Rodríguez, C. (Carmen); Triana, P. (Paloma); Hervas-Stubbs, S. (Sandra); Reina, G. (Gabriel); Andrea, C.E. (Carlos Eduardo) de; Basu, D. (Dipanjan); Redondo-Bellón, P. (Pedro)
    To the Editor: Some patients with congenital melanocytic nevi (CMN) present progressive growth and thickening, extracutaneous involvement (neurocutaneous melanocytosis, NCM) or neoplastic transformation (melanoma); and others remain stable or even regress. There are no markers to assess progression or follow-up. Recently, we found S-100, a protein which acts on cell differentiation and proliferation, elevated in CMN.1 S-100 is a ligand of the RAGE pathway (related to the MAPK-pathway), and low serum levels of soluble-RAGE were related to poor survival in melanoma.2 Also SOX10, expressed in melanocytes with high specificity, is useful in detection, prognosis and treatment assessment of melanoma.3 We explored if S-100, RAGE and SOX10 serum levels vary in children’s CMN and assessed clinical or pathological correlations.