{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T09:12:47Z","timestamp":1769677967574,"version":"3.49.0"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background\/Objectives: Melanoma is an aggressive skin malignancy, and the majority of deaths associated with melanoma result from malignant skin lesions. Our study aims to evaluate the expression of the markers CD133 and NANOG, associated with tumor stem cells, and to analyze their link with epidemiological and histological parameters, thus contributing to early diagnosis and the development of targeted therapies. Methods: We performed a retrospective study in the Mure\u0219 Clinical County Hospital, Romania, which included 66 cases of melanoma: 50 primary cutaneous melanomas, 10 metastases, and 6 local recurrences. CD133 and NANOG marker expression was assessed by immunohistochemistry and quantified using the H score. Statistical analyses were applied to determine the correlations between marker expression and clinicopathological parameters. Results: CD133 expression was identified in six cases (12%) of primary melanoma, with a mean H-Score of 29, and was associated with an increased Breslow index and a higher number of mitoses. NANOG expression was positive in 30 cases (60%) of primary melanoma, with a median H-Score of 15 and with increased expression observed in cases with pagetoid migration and lesions in situ. In metastases, eight cases (80%) were positive for NANOG and four (40%) for CD133. Local recurrences showed positive expression for NANOG in four cases (66%). Conclusions: The expression of CD133 and NANOG markers highlights the role of tumor stem cells in melanoma progression. Early identification of these markers could improve diagnosis and treatment, including the application of targeted therapies.<\/jats:p>","DOI":"10.3390\/medicina60101658","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T08:16:42Z","timestamp":1728548202000},"page":"1658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterizing CD133 and NANOG Expression in Melanoma: Associations with Histological and Epidemiological Parameters"],"prefix":"10.3390","volume":"60","author":[{"given":"Adrian-Hora\u021biu","family":"Sab\u0103u","sequence":"first","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"},{"name":"Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raluca","family":"Niculescu","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"},{"name":"Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-2433","authenticated-orcid":false,"given":"Iuliu-Gabriel","family":"Cocuz","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"},{"name":"Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreea-C\u0103t\u0103lina","family":"Tinca","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"},{"name":"Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreea Raluca","family":"Sz\u00f6ke","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"},{"name":"Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Andreea","family":"Lazar","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana Maria","family":"Chiorean","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"},{"name":"Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-0121","authenticated-orcid":false,"given":"Corina Eugenia","family":"Budin","sequence":"additional","affiliation":[{"name":"Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Pneumology Department, Clinical County Hospital Mure\u0219, 540136 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3734-5305","authenticated-orcid":false,"given":"Alexandru Nicu\u0219or","family":"Tomu\u021b","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ovidiu Simion","family":"Cotoi","sequence":"additional","affiliation":[{"name":"Pathology Department, Mures Clinical County Hospital, 540011 Targu Mures, Romania"},{"name":"Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology \u201cGeorge Emil Palade\u201d of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gordon, L.G., Leung, W., Johns, R., McNoe, B., Lindsay, D., Merollini, K.M.D., Elliott, T.M., Neale, R.E., Olsen, C.M., and Pandeya, N. (2022). Estimated Healthcare Costs of Melanoma and Keratinocyte Skin Cancers in Australia and Aotearoa New Zealand in 2021. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19063178"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Giurc\u0103neanu, C., and Orzan, O.A. (2024). Recent-Onset Melanoma and the Implications of the Excessive Use of Tanning Devices\u2014Case Report and Review of the Literature. Medicina, 60.","DOI":"10.3390\/medicina60010187"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zaharie, F.A., Vesa, \u0218.C., and Cosgarea, R. (2024). PRAME Immunohistochemistry in Thin Melanomas Compared to Melanocytic Nevi. Diagnostics, 14.","DOI":"10.3390\/diagnostics14182015"},{"key":"ref_4","first-page":"937","article-title":"The use of immunohistochemical staining in Mohs micrographic surgery for melanoma: A systematic review","volume":"313","author":"Xia","year":"2021","journal-title":"Arch. Dermatol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tinca, A.C., Moraru, R., Cocuz, I.G., \u0218incu, M.C., Niculescu, R., Sab\u0103u, A.H., Chiorean, D.M., Szoke, A.R., Morariu, S.-H., and Cotoi, O.S. (2022). Actualities in the Morphology and Immunohistochemistry of Cutaneous and Ocular Melanoma: What Lies Ahead? A Single-Centre Study. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102500"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kim, H.J., and Kim, Y.H. (2024). Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052984"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Valdez-Salazar, F., Jim\u00e9nez-Del Rio, L.A., Padilla-Guti\u00e9rrez, J.R., Valle, Y., Mu\u00f1oz-Valle, J.F., and Vald\u00e9s-Alvarado, E. (2024). Advances in Melanoma: From Genetic Insights to Therapeutic Innovations. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081851"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Castellani, G., Buccarelli, M., Arasi, M.B., Rossi, S., Pisanu, M.E., Bellenghi, M., Lintas, C., and Tabolacci, C. (2023). BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers. Cancers, 15.","DOI":"10.3390\/cancers15164026"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"566","DOI":"10.3892\/ol.2021.12827","article-title":"Effect of melanoma stem cells on melanoma metastasis (Review)","volume":"22","author":"Yin","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Al Hmada, Y., Brodell, R.T., Kharouf, N., Flanagan, T.W., Alamodi, A.A., Hassan, S.-Y., Shalaby, H., Hassan, S.-L., Haikel, Y., and Megahed, M. (2024). Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells. Cancers, 16.","DOI":"10.3390\/cancers16020470"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jing, N., Gao, W.Q., and Fang, Y.X. (2021). Regulation of Formation, Stemness and Therapeutic Resistance of Cancer Stem Cells. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.641498"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12943-020-01291-6","article-title":"Taking the Myc out of cancer: Toward therapeutic strategies to directly inhibit c-Myc","volume":"20","author":"Madden","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8278","DOI":"10.3390\/curroncol30090601","article-title":"An Overview of CD133 as a Functional Unit of Prognosis and Treatment Resistance in Glioblastoma","volume":"30","author":"Jagasia","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Monge, C., Dianzani, C., Barrera, G., and Muzio, G. (2021). Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies. Antioxidants, 10.","DOI":"10.3390\/antiox10121942"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Smith, J., Field, M., and Sugaya, K. (2023). Suppression of NANOG Expression Reduces Drug Resistance of Cancer Stem Cells in Glioblastoma. Genes, 14.","DOI":"10.3390\/genes14061276"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12943-016-0578-3","article-title":"Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma","volume":"16","author":"Kumar","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1002\/stem.2007","article-title":"Concise Review: NANOG in Cancer Stem Cells and Tumor Development: An Update and Outstanding Questions","volume":"33","author":"Jeter","year":"2015","journal-title":"Stem Cells"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kaur, J., and Bhattacharyya, S. (2021). Cancer Stem Cells: Metabolic Characterization for Targeted Cancer Therapy. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.756888"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s40257-017-0292-y","article-title":"MEK Inhibitors in the Treatment of Metastatic Melanoma and Solid Tumors","volume":"18","author":"Grimaldi","year":"2017","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.cell.2008.02.007","article-title":"Mechanisms of Asymmetric Stem Cell Division","volume":"132","author":"Knoblich","year":"2008","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e130510","DOI":"10.1172\/jci.insight.130510","article-title":"Asymmetric Cell Division Promotes Therapeutic Resistance in Glioblastoma Stem Cells","volume":"6","author":"Hitomi","year":"2021","journal-title":"JCI Insight"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mohan, A., Raj, R., Mohan, G., KP, P., and Maliekal, T.T. (2021). Reporters of Cancer Stem Cells as a Tool for Drug Discovery. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.669250"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Papaccio, F., and Papaccio, G. (2024). ALDH Activity Assay: A Method for Cancer Stem Cell (CSC) Identification and Isolation. Cancer Stem Cells. Methods in Molecular Biology, Springer.","DOI":"10.1007\/978-1-0716-3730-2"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fernando, W., Venkatesh, J., and Marcato, P. (2023). The Expanding Role of Cancer Stem Cell Marker ALDH1A3 in Cancer and Beyond. Cancers, 15.","DOI":"10.3390\/cancers15020492"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1634\/stemcells.2008-0601","article-title":"The Stem Cell-Associated Antigen CD133 (Prominin-1) Is a Molecular Therapeutic Target for Metastatic Melanoma","volume":"26","author":"Rappa","year":"2008","journal-title":"Stem Cells"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s40259-019-00370-5","article-title":"Mission Possible: Advances in MYC Therapeutic Targeting in Cancer","volume":"33","author":"Sears","year":"2019","journal-title":"BioDrugs"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s40487-022-00205-4","article-title":"Expression and Prognostic Significance of Stem Cell Marker CD133 in Survival Rate of Patients with Colon Cancer","volume":"10","author":"Ehteram","year":"2022","journal-title":"Oncol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kuo, L.W., Sykora, P., and Rosenthal, D.S. (2024). CD133 Stimulates Cell Proliferation via the Upregulation of Amphiregulin in Melanoma. Cells, 13.","DOI":"10.3390\/cells13090777"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhang, L., Li, D., and Zheng, W. (2023). TRRAP Enhances Cancer Stem Cell Characteristics by Regulating NANOG Protein Stability in Colon Cancer Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076260"},{"key":"ref_30","first-page":"1234","article-title":"Insights into the Nanog Gene: A Propeller for Stemness in Primitive Stem Cells","volume":"19","author":"Zhang","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sukhikh, G., and Fatkhudinov, T. (2023). EndoNet: A Model for the Automatic Calculation of H-Score on Histological Slides. Informatics, 10.","DOI":"10.3390\/informatics10040090"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Aljitawi, O., and Van Veldhuizen, P. (2022). Prostate Cancer Stem Cells: The Role of CD133. Cancers, 14.","DOI":"10.3390\/cancers14215448"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tinca, A.C., Szoke, A.R., Lazar, B.A., Sz\u00e1sz, E.A., Tomu\u021b, A.N., Sab\u0103u, A.H., Cocuz, I.-G., Cotoi, T.-C., Niculescu, R., and Chiorean, D.M. (2024). H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084335"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/10\/1658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:10:36Z","timestamp":1760112636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/10\/1658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,10]]},"references-count":33,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["medicina60101658"],"URL":"https:\/\/doi.org\/10.3390\/medicina60101658","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,10]]}}}