{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:36:25Z","timestamp":1792816585506,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RUDN University Scientific Projects Grant System","award":["210506-0-000"],"award-info":[{"award-number":["210506-0-000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Background: Mast cells, key effectors of the innate immune system, are known to participate in various stages of tumor progression, including inflammation, angiogenesis, and extracellular matrix remodeling. Their role in melanoma, particularly in relation to Breslow thickness, pT stage, and AJCC staging, remains unclear. This study aims to quantitatively and phenotypically assess mast cell infiltration in cutaneous melanoma at different stages of progression, focusing on Tryptase- and Chymase-positive subtypes. Methods: This retrospective multicenter study included 124 patients with cutaneous melanoma (AJCC 8th edition, stages IA\u2013IIIC). Histological sections were stained with hematoxylin and eosin, and mast cells were visualized using toluidine blue and immunohistochemistry with anti-Tryptase and anti-Chymase antibodies. Mast cells were counted manually in intratumoral and peritumoral regions by two independent observers. Quantitative data were analyzed using non-parametric tests and presented as median [Q1\u2013Q3]. Results: Histological examination of 124 melanoma samples confirmed typical features of cutaneous melanoma, with nodular melanoma being the most common subtype (68 cases, 54.8%) and the lower extremities identified as the predominant tumor location (47 cases, 37.9%). Toluidine blue staining verified the presence of mast cells in both intratumoral and peritumoral compartments, with the highest density observed in early-stage melanomas. Immunohistochemical analysis identified both Tryptase+ and Chymase+ mast cells. The intratumoral number of Tryptase+ cells declined from 17 [14\u201319] per HPF at AJCC stage IA to 6 [5\u20137] per HPF at stage IIIC, while Chymase+ mast cells decreased from 14 [11\u201316] per HPF to 2 [1\u20133] per HPF over the same stages. Peritumoral counts also showed a downward trend, although less pronounced. Overall, the most significant reduction was observed in Chymase+ mast cells, suggesting their potential role as markers of melanoma progression. Conclusions: This study highlights the dynamic changes in mast cell populations in cutaneous melanoma, with a pronounced decrease in Chymase+ mast cells as the tumor progresses. Further research is needed to explore the mechanistic role of mast cells and their phenotypic shifts in melanoma progression.<\/jats:p>","DOI":"10.3390\/cimb47090752","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T12:08:16Z","timestamp":1757678896000},"page":"752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phenotypic and Quantitative Characterization of Mast Cells in Cutaneous Melanoma: Correlation with Staging Metrics"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8447-2600","authenticated-orcid":false,"given":"Grigory","family":"Demyashkin","sequence":"first","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky, 3, 125284 Moscow, Russia"},{"name":"Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya st., 8\/2, 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8347-4556","authenticated-orcid":false,"given":"Dmitrii","family":"Atiakshin","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya st., 6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2073-3699","authenticated-orcid":false,"given":"Kirill","family":"Silakov","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya st., 6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-7454","authenticated-orcid":false,"given":"Vladimir","family":"Shchekin","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky, 3, 125284 Moscow, Russia"},{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya st., 6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Bobrov","sequence":"additional","affiliation":[{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya st., 6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Abramova","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky, 3, 125284 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-1020","authenticated-orcid":false,"given":"Matvey","family":"Vadyukhin","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky, 3, 125284 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Borovaya","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky, 3, 125284 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Blinova","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Immunohistochemistry, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya st., 8\/2, 119048 Moscow, Russia"},{"name":"Department of Fundamental Medicine, Institute for Physics and Engineering in Biomedicine, National Research Nuclear University MEPhI, Kashirskoe shosse, 31, 115409 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Shegay","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky, 3, 125284 Moscow, Russia"},{"name":"Department of Urology and Operative Nephrology, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya str.6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Kaprin","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky, 3, 125284 Moscow, Russia"},{"name":"Department of Urology and Operative Nephrology, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya str.6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1001\/jamadermatol.2022.0160","article-title":"Global Burden of Cutaneous Melanoma in 2020 and Projections to 2040","volume":"158","author":"Arnold","year":"2022","journal-title":"JAMA Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.jaad.2023.11.003","article-title":"Melanoma Incidence and Mortality: Exploring the Impact of Regional UV Radiation and Socioeconomic Status in the Context of Breslow Thickness","volume":"90","author":"Maghfour","year":"2023","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Didier, A.J., Nandwani, S., Watkins, D., Fahoury, A.M., Campbell, A., Craig, D.J., Vijendra, D., and Parquet, N. (2024). Patterns and trends in melanoma mortality in the United States, 1999\u20132020. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12426-z"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kharouf, N., Flanagan, T.W., Hassan, S.-Y., Shalaby, H., Khabaz, M., Hassan, S.-L., Megahed, M., Haikel, Y., Santourlidis, S., and Hassan, M. (2023). Tumor Microenvironment as a Therapeutic Target in Melanoma Treatment. Cancers, 15.","DOI":"10.3390\/cancers15123147"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mazurkiewicz, J., Simiczyjew, A., Dratkiewicz, E., Zi\u0119tek, M., Matkowski, R., and Nowak, D. (2021). Stromal Cells Present in the Melanoma Niche Affect Tumor Invasiveness and Its Resistance to Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020529"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"176103","DOI":"10.1016\/j.ejphar.2023.176103","article-title":"Role of mast cells activation in the tumor immune microenvironment and immunotherapy of cancers","volume":"960","author":"Guo","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Shi, S., Ye, L.Y., Yu, X., Jin, K., and Wu, W. (2022). Focus on mast cells in the tumor microenvironment: Current knowledge and future directions. Biochim. Biophys. Acta Rev. Cancer, 1878.","DOI":"10.1016\/j.bbcan.2022.188845"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.5115\/acb.19.181","article-title":"Tumor associated mast cells: Biological roles and therapeutic applications","volume":"53","author":"Saxena","year":"2020","journal-title":"Anat. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Segura-Villalobos, D., Ram\u00edrez-Moreno, I.G., Mart\u00ednez-Aguilar, M., Ibarra-S\u00e1nchez, A., Mu\u00f1oz-Bello, J.O., Anaya-Rubio, I., Padilla, A., Mac\u00edas-Silva, M., Lizano, M., and Gonz\u00e1lez-Espinosa, C. (2022). Mast Cell\u2013Tumor Interactions: Molecular Mechanisms of Recruitment, Intratumoral Communication and Potential Therapeutic Targets for Tumor Growth. Cells, 11.","DOI":"10.3390\/cells11030349"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1158\/0008-5472.CAN-19-3596","article-title":"Infiltrating Mast Cell-Mediated Stimulation of Estrogen Receptor Activity in Breast Cancer Cells Promotes the Luminal Phenotype","volume":"80","author":"Majorini","year":"2020","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hou, Y., Wang, Q., Su, L., Zhu, Y., Xiao, Y., and Feng, F. (2023). Increased tumor-associated mast cells facilitate thyroid cancer progression by inhibiting CD8+ T cell function through galectin-9. Braz. J. Med. Biol. Res., 56.","DOI":"10.1590\/1414-431x2023e12370"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ribatti, D. (2024). New insights into the role of mast cells as a therapeutic target in cancer through the blockade of immune checkpoint inhibitors. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1373230"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s12016-019-08769-2","article-title":"Mast Cell Biology at Molecular Level: A Comprehensive Review","volume":"58","author":"Komi","year":"2020","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Noto, C.N., Hoft, S.G., and DiPaolo, R.J. (2021). Mast Cells as Important Regulators in Autoimmunity and Cancer Development. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.752350"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s12016-019-08753-w","article-title":"Role of Mast Cells in Shaping the Tumor Microenvironment","volume":"58","author":"Komi","year":"2020","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nishimura, H., Jin, D., Kinoshita, I., Taniuchi, M., Higashino, M., Terada, T., Takai, S., and Kawata, R. (2023). Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098267"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Takai, S., and Jin, D. (2022). Pathophysiological Role of Chymase-Activated Matrix Metalloproteinase-9. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102499"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lichterman, J.N., and Reddy, S.M. (2021). Mast Cells: A New Frontier for Cancer Immunotherapy. Cells, 10.","DOI":"10.3390\/cells10061270"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Audero, M.M., Prevarskaya, N., and Fiorio Pla, A. (2022). Ca2+ Signalling and Hypoxia\/Acidic Tumour Microenvironment Interplay in Tumour Progression. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202206.0034.v1"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ribatti, D. (2024). Tryptase and tumor angiogenesis. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1500482"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hanes, M.R., Giacomantonio, C.A., and Marshall, J.S. (2021). Mast Cells and Skin and Breast Cancers: A Complicated and Microenvironment-Dependent Role. Cells, 10.","DOI":"10.3390\/cells10050986"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.4149\/neo_2022_221014N1020","article-title":"Mast cells as a tumor microenvironment factor associated with the aggressiveness of prostate cancer","volume":"69","author":"Zadvornyi","year":"2022","journal-title":"Neoplasma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41420-024-02258-y","article-title":"Mast cells: Key players in digestive system tumors and their interactions with immune cells","volume":"11","author":"Shu","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1158\/0008-5472.CAN-22-3140","article-title":"Elevated Mast Cell Abundance is Associated with Enrichment of CCR2+ Cytotoxic T cells and Favorable Prognosis in Lung Adenocarcinoma","volume":"83","author":"Fan","year":"2023","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mo, S., Zong, L., Chen, X., Chang, X., Lu, Z., Yu, S., and Chen, J. (2021). Supplementary Material for: High Mast Cell Density Predicts a Favorable Prognosis in Patients with Pancreatic Neuroendocrine Neoplasms, Karger Publishers.","DOI":"10.1159\/000521651"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Annese, T., Tamma, R., Bozza, M., Zito, A., and Ribatti, D. (2022). Autocrine\/Paracrine Loop Between SCF+\/c-Kit+ Mast Cells Promotes Cutaneous Melanoma Progression. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.794974"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/9\/752\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:44:33Z","timestamp":1760035473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/9\/752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["cimb47090752"],"URL":"https:\/\/doi.org\/10.3390\/cimb47090752","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,12]]}}}