<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Morphology</journal-id><journal-title-group><journal-title xml:lang="en">Morphology</journal-title><trans-title-group xml:lang="ru"><trans-title>Морфология</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1026-3543</issn><issn publication-format="electronic">2949-2556</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">676878</article-id><article-id pub-id-type="doi">10.17816/morph.676878</article-id><article-id pub-id-type="edn">RABDZT</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original Study Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные исследования</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Diagnostic and prognostic value of immunohistochemical markers HMB-45, Melan-A/MART-1, and S100 in different histological subtypes of melanoma</article-title><trans-title-group xml:lang="ru"><trans-title>Диагностическая и прогностическая ценность иммуногистохимических маркеров HMB-45, Melan-A/MART-1 и S100 при различных гистологических подтипах меланомы</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>免疫组化标记物HMB-45、Melan-A/MART-1和S100在不同类型黑色素瘤组织学亚型中的诊断和预后价值</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0000-2073-3699</contrib-id><name-alternatives><name xml:lang="en"><surname>Silakov</surname><given-names>Kirill A.</given-names></name><name xml:lang="ru"><surname>Силаков</surname><given-names>Кирилл Александрович</given-names></name><name xml:lang="zh"><surname>Silakov</surname><given-names>Kirill A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>k_30_10@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0001-8535-999X</contrib-id><name-alternatives><name xml:lang="en"><surname>Demenkova</surname><given-names>Ekaterina Yu.</given-names></name><name xml:lang="ru"><surname>Деменкова</surname><given-names>Екатерина Юрьевна</given-names></name><name xml:lang="zh"><surname>Demenkova</surname><given-names>Ekaterina Yu.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>demenkate@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3763-7454</contrib-id><contrib-id contrib-id-type="spin">3664-8044</contrib-id><name-alternatives><name xml:lang="en"><surname>Shchekin</surname><given-names>Vladimir I.</given-names></name><name xml:lang="ru"><surname>Щекин</surname><given-names>Владимир Иванович</given-names></name><name xml:lang="zh"><surname>Shchekin</surname><given-names>Vladimir I.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>Dr.shchekin@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7374-0374</contrib-id><contrib-id contrib-id-type="spin">3058-6092</contrib-id><name-alternatives><name xml:lang="en"><surname>Bobrov</surname><given-names>Maksim A.</given-names></name><name xml:lang="ru"><surname>Бобров</surname><given-names>Максим Александрович</given-names></name><name xml:lang="zh"><surname>Bobrov</surname><given-names>Maksim A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><email>M.a.bobrov@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8447-2600</contrib-id><contrib-id contrib-id-type="spin">5157-0177</contrib-id><name-alternatives><name xml:lang="en"><surname>Demyashkin</surname><given-names>Grigory A.</given-names></name><name xml:lang="ru"><surname>Демяшкин</surname><given-names>Григорий Александрович</given-names></name><name xml:lang="zh"><surname>Demyashkin</surname><given-names>Grigory A.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci. (Medicine)</p></bio><bio xml:lang="ru"><p>д-р мед. наук</p></bio><bio xml:lang="zh"><p>Dr. Sci. (Medicine)</p></bio><email>dr.dga@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Peoples’ Friendship University of Russia</institution></aff><aff><institution xml:lang="ru">Российский университет дружбы народов им. П. Лумумбы</institution></aff><aff><institution xml:lang="zh">Peoples’ Friendship University of Russia</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">National Medical Research Radiological Center of the Ministry of Health of the Russian Federation</institution></aff><aff><institution xml:lang="ru">Национальный медицинский исследовательский центр радиологии Минздрава России</institution></aff><aff><institution xml:lang="zh">National Medical Research Radiological Center of the Ministry of Health of the Russian Federation</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-07-04" publication-format="electronic"><day>04</day><month>07</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2025-10-23" publication-format="electronic"><day>23</day><month>10</month><year>2025</year></pub-date><volume>163</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><issue-title xml:lang="zh"/><fpage>353</fpage><lpage>362</lpage><history><date date-type="received" iso-8601-date="2025-03-05"><day>05</day><month>03</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-04-13"><day>13</day><month>04</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, Эко-Вектор</copyright-statement><copyright-statement xml:lang="zh">Copyright ©; 2025,</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2028-10-23"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref></license></permissions><self-uri xlink:href="https://j-morphology.com/1026-3543/article/view/676878">https://j-morphology.com/1026-3543/article/view/676878</self-uri><abstract xml:lang="en"><p><bold>BACKGROUND: </bold>Melanoma is a malignant neoplasm that arises from melanocytes, which are melanin-producing cells primarily found in the skin. Although rare, melanoma is highly aggressive. In 2023, 13,270 cases of skin melanoma were identified in Russia. The primary risk factor is excessive exposure to ultraviolet radiation. Immunohistochemical studies using markers such as HMB-45 (Human Melanoma Black-45), Melan-A/MART-1 (Melanoma Antigen Recognized by T Cells 1), and S100 are crucial for diagnosing skin melanoma, improving the accuracy of tumor detection, and optimizing treatment.</p> <p><bold>AIM: </bold>This study aimed to assess the prognostic significance of melanocytic markers HMB-45, Melan-A/MART-1, and S100 in skin melanoma, taking into account tumor histological subtypes and stages according to the pTNM classification.</p> <p><bold>METHODS:</bold> Skin melanoma samples from patients (<italic>n</italic> = 117) were assessed using immunohistochemistry with antibodies to HMB-45, Melan-A/MART-1, and S100. The results were interpreted based on the histological subtype of the tumor and the Breslow thickness, which was used to determine the disease stage.</p> <p><bold>RESULTS: </bold>The count of atypical melanoma cells, considering the histological subtype of the tumor, showed that the S100 marker had the highest sensitivity (91.2%) compared to Melan-A/MART-1 and HMB-45, especially in desmoplastic melanoma. Moreover, S100 and Melan-A/MART-1 demonstrated stable staining regardless of the degree of invasion, whereas the number of HMB-45-positive atypical melanocytes increased as the tumor progressed according to the pTNM classification.</p> <p><bold>CONCLUSION: </bold>Immunohistochemical analysis of various histological subtypes of skin melanoma revealed stable expression of S100, Melan-A/MART-1, and HMB-45 proteins in superficial spreading and nodular tumors. In desmoplastic melanoma, the expression of Melan-A/MART-1 and HMB-45 was absent, whereas S100 expression remained. The proportion of S100- and Melan-A/MART-1-positive atypical cells was independent of the degree of tumor invasion (according to pTNM stages). The percentage of HMB-45-positive atypical melanocytes increased proportionally with the thickness of invasion, supporting its prognostic significance.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Обоснование. </bold>Меланома — злокачественное новообразование, развивающееся из меланоцитов — клеток, синтезирующих меланин и локализующихся преимущественно в коже. Несмотря на редкость, меланома обладает высокой агрессивностью. В 2023 году в России выявлено 13 270 случаев меланомы кожи. Основным фактором риска является избыточное воздействие ультрафиолетового излучения. Иммуногистохимические исследования с использованием маркеров HMB-45 (Human Melanoma Black-45), Melan-A/MART-1 (Melanoma Antigen Recognized by T cells 1) и S100 играют ключевую роль в диагностике меланомы кожи и позволяют повысить точность выявления опухоли и оптимизировать лечение.</p> <p><bold>Цель </bold>— оценить прогностическую значимость меланоцитарных маркеров HMB-45, Melan-A/MART-1 и S100 при меланоме кожи с учётом гистологических подтипов опухоли и стадий согласно классификации pTNM.</p> <p><bold>Методы. </bold>Образцы меланомы кожи пациентов (<italic>n</italic> = 117) исследовали иммуногистохимическим методом с использованием антител к HMB-45, Melan-A/MART-1 и S100. При интерпретации результатов учитывали гистологический подтип опухоли и толщину инвазии по Breslow, на основании которой определяли стадию заболевания.</p> <p><bold>Результаты. </bold>Подсчёт атипичных клеток меланомы с учётом её гистологического подтипа показал наибольшую чувствительность маркера S100 (91,2%) по сравнению с Melan-A/MART-1 и HMB-45, особенно при десмопластическом типе опухоли. Кроме того, маркеры S100 и Melan-A/MART-1 демонстрируют стабильное окрашивание независимо от степени инвазии, в то время как количество HMB-45-позитивных атипичных меланоцитов увеличивается по мере прогрессирования опухоли в соответствии с классификацией по системе pTNM (Tumor, Node, Metastasis).</p> <p><bold>Заключение.</bold> При иммуногистохимическом исследовании различных гистологических подтипов меланомы кожи обнаружена стабильная экспрессия белков S100, Melan-A/MART-1 и HMB-45 в поверхностно-распространяющейся и узловой формах опухоли. При десмопластическом подтипе меланомы кожи экспрессия Melan-A/MART-1 и HMB- 45 отсутствует, тогда как экспрессия S100 сохраняется. Доля S100- и Melan-A/MART-1-позитивных атипичных клеток не зависит от степени инвазии опухоли (в соответствии со стадиями pTNM). В то же время, процент HMB-45-позитивных атипичных меланоцитов пропорционально увеличивается с ростом толщины инвазии, что не исключает его прогностическую значимость.</p></trans-abstract><trans-abstract xml:lang="zh"><p><bold>论证。</bold>黑色素瘤是一种恶性肿瘤，源自黑色素细胞——这些细胞主要位于皮肤中，负责合成黑色素。尽管这种病相对罕见，但其侵袭性很强。在2023年，俄罗斯确诊皮肤黑色素瘤病例为13,270例。过度的紫外线辐射是主要的风险因素。使用HMB-45（Human Melanoma Black-45）、Melan-A/MART-1（Melanoma Antigen Recognized by T cells 1）和S100等免疫组化研究方法在黑色素瘤的诊断中起着关键作用，能提高肿瘤的检测准确性并优化治疗方案。</p> <p><bold>目的。</bold>评估皮肤黑色素瘤在不同组织学亚型和pTNM分期下，HMB-45、Melan-A/MART-1和S100黑色素细胞标记物的预后价值。</p> <p><bold>方法。</bold>对皮肤黑色素瘤样本（n = 117）进行免疫组化分析，使用了针对HMB-45、Melan-A/MART-1和S100的抗体。结果的解释基于肿瘤的组织学亚型和Breslow浸润厚度，并依据此确定了疾病的分期。</p> <p><bold>结果。</bold>通过对不同组织学亚型黑色素瘤中不典型细胞的计数，发现S100标记物的灵敏度最高（91.2%），尤其是在类纤维化型肿瘤中，较Melan-A/MART-1和HMB-45更为敏感。与此同时，S100和Melan-A/MART-1标记物无论在浸润程度上如何，都会保持稳定的染色，而HMB-45阳性不典型黑色素细胞的数量随着肿瘤进展和pTNM（Tumor, Node, Metastasis）分期的增加而增加。</p> <p><bold>结论。</bold>在免疫组化研究中，不同组织学亚型的皮肤黑色素瘤表现出S100、Melan-A/MART-1和HMB-45的稳定表达，特别是在表浅扩展型和结节型肿瘤中。对于纤维化型皮肤黑色素瘤，Melan-A/MART-1和HMB-45的表达缺失，而S100表达保持不变。S100和Melan-A/MART-1阳性不典型细胞的比例不受肿瘤浸润程度的影响（依据pTNM分期）。然而，HMB-45阳性不典型黑色素细胞的百分比随着浸润厚度的增加而增加，因此它具有较强的预后意义。</p></trans-abstract><kwd-group xml:lang="en"><kwd>skin melanoma</kwd><kwd>immunohistochemistry</kwd><kwd>S100</kwd><kwd>Melan-A/MART-1</kwd><kwd>HMB-45</kwd><kwd>Breslow thickness</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>меланома кожи</kwd><kwd>иммуногистохимия</kwd><kwd>S100</kwd><kwd>Melan-A/MART-1</kwd><kwd>HMB-45</kwd><kwd>толщина инвазии по Breslow</kwd></kwd-group><kwd-group xml:lang="zh"><kwd>皮肤黑色素瘤</kwd><kwd>免疫组化</kwd><kwd>S100</kwd><kwd>Melan-A/MART-1</kwd><kwd>HMB-45</kwd><kwd>Breslow浸润厚度</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–263. doi: 10.3322/caac.21834 EDN: FRJDQH</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Lindberg MR. Diagnostic Pathology: Normal Histology. 3rd ed. Elsevier; 2022. ISBN: 9780323834155</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Kaprin AD, Starinskiy VV, Shakhzadova AO, editors. Malignant Neoplasms in Russia in 2023 (Incidence and Mortality). Moscow: P.A. Hertzen Moscow Oncology Research Institute — Branch of the National Medical Research Center of Radiology, Ministry of Health of the Russian Federation, 2024. ISBN: 978-5-85502-298-8</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Eduardo Calonje J, Brenn T, Lazar AJ, Billings SD. McKee’s Pathology of the Skin. 5th ed. Elsevier; 2019. ISBN: 9780702069833</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>WHO Classification of Tumours Editorial Board. Skin tumours [Internet]. 5th ed. Lyon: International Agency for Research on Cancer; 2023 [cited 2025 Feb 14]. Available at: https://tumourclassification.iarc.who.int/chapters/64</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Ho J, Collie CJ. What’s new in dermatopathology 2023: WHO 5th edition updates. J Pathol Transl Med. 2023;57(6):337–340. doi: 10.4132/jptm.2023.09.22 EDN: YOOZND</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Tuffaha MSA, Guski H, Kristiansen G. Immunohistochemistry in tumor diagnostics. Springer; 2023. doi: 10.1007/978-3-031-45024-2 ISBN: 978-3-031-45023-5</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Gershenwald JE, Scolyer RA, Hess KR, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472–492. doi: 10.3322/caac.21409</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Saleem A, Narala S, Raghavan SS. Immunohistochemistry in melanocytic lesions: Updates with a practical review for pathologists. Semin Diagn Pathol. 2022;39(4):239–247. doi: 10.1053/j.semdp.2021.12.003 EDN: MMGQKG</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Plaza JA, Bonneau P, Prieto V, et al. Desmoplastic melanoma: an updated immunohistochemical analysis of 40 cases with a proposal for an additional panel of stains for diagnosis. J Cutan Pathol. 2016;43(4):313–323. doi: 10.1111/cup.12654</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Olaoba OT, Kadasah S, Vetter SW, Leclerc E. RAGE signaling in melanoma tumors. Int J Mol Sci. 2020;21(23):8989. doi: 10.3390/ijms21238989</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Abramova OB, Demyashkin GA, Drozhzhina VV, et al. On the pathomorphological pattern of the efficiency of photodynamic therapy of murine melanoma B16 using a new photosensitizer based on Chlorin e6 conjugate with a Prostate-specific membrane antigen. Molecules. 2022;27(11):3445. doi: 10.3390/molecules27113445 EDN: LAERII</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Pop AM, Monea M, Olah P, et al. The importance of immunohistochemistry in the evaluation of tumor depth of primary cutaneous melanoma. Diagnostics (Basel). 2023;13(6):1020. doi: 10.3390/diagnostics13061020 EDN: EONIKP</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Kamyab-Hesary K, Ghanadan A, Balighi K, et al. Immunohistochemical staining in the assessment of melanoma tumor thickness. Pathol Oncol Res. 2020;26(2):885–891. doi: 10.1007/s12253-019-00635-y EDN: LKTYOA</mixed-citation></ref></ref-list></back></article>
