{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T07:32:02Z","timestamp":1771745522881,"version":"3.50.1"},"reference-count":91,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Medicina"],"abstract":"<jats:p>Background\u00a0and Objectives: Cutaneous melanomas are highly aggressive and prevalent malignancies that often require complex diagnostic and therapeutic procedures. Mounting evidence supports the utility of several biomarkers for improving diagnostic accuracy and treatment decisions. In this study, we aimed to evaluate the correlations between various histopathological and immunohistochemical markers to better understand melanoma development and its subsequent behavior. Materials and Methods: We conducted a retrospective study on 59 patients diagnosed with cutaneous melanoma to establish the significant correlations between clinical, histopathological, and immunohistochemical markers. Results: The mean age of the patients was 60.15 years, with a male-to-female ratio of 1.27:1. Our results demonstrate significant correlations between proliferative activity, evaluated both as mitotic counts and Ki-67 index, and clinicopathological parameters. Other significant correlations between melanoma immunohistochemical markers such as Melan-A, HMB45, S100 or PRAME and Breslow depth highlight their potential not only for diagnostic but also for prognostic purposes. Additionally, the significant negative correlations between p16 and patient age, Breslow depth, and the Ki-67 index emphasize the predictive value of this still insufficiently described parameter. Conclusions: Taken together, these observations underscore the importance of integrating biomarker evaluation into melanoma management, enabling more precise prognostication and the development of individualized treatment strategies.<\/jats:p>","DOI":"10.3390\/medicina61101733","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:39:42Z","timestamp":1758710382000},"page":"1733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Key Biomarker Correlations in Cutaneous Melanoma: Implications for Diagnostic, Prognostic, and Therapeutic Strategies\u2014A Retrospective Single-Centered Study"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3919-862X","authenticated-orcid":false,"given":"Mariana","family":"Costache","sequence":"first","affiliation":[{"name":"Department of Pathology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Pathology, University Emergency Hospital, 050098 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ancu\u021ba-Augustina","family":"Gheorghi\u015fan-G\u0103l\u0103\u021beanu","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology and Histology (Ret.), Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Parhon National Institute of Endocrinology (Ret.), 011863 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7058-0963","authenticated-orcid":false,"given":"Diana","family":"Derewicz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Pediatric Hematology and Oncology, Marie Sklodowska Curie Clinical Emergency Hospital, 041447 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u0103t\u0103lin","family":"C\u00eerstoiu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Traumatology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 030167 Bucharest, Romania"},{"name":"Department of Orthopedics and Traumatology, University Emergency Hospital, 050098 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreea","family":"Ilie\u0219iu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Pathology, University Emergency Hospital, 050098 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/exd.12618","article-title":"The role of melanin pigment in melanoma","volume":"24","author":"Slominski","year":"2015","journal-title":"Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/healthcare2010001","article-title":"Malignant Melanoma","volume":"2","author":"Perera","year":"2013","journal-title":"Healthcare"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0933-3657(02)00087-8","article-title":"A multiple classifier system for early melanoma diagnosis","volume":"27","author":"Sboner","year":"2003","journal-title":"Artif. Intell. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Buja, A., Bardin, A., Damiani, G., Zorzi, M., De Toni, C., Fusinato, R., Spina, R., Vecchiato, A., Del Fiore, P., and Mocellin, S. (2021). Prognosis for Cutaneous Melanoma by Clinical and Pathological Profile: A Population-Based Study. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.737399"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"942","DOI":"10.2214\/AJR.16.16800","article-title":"Clinical and Imaging Features of Noncutaneous Melanoma","volume":"208","author":"Wong","year":"2017","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_6","first-page":"135","article-title":"The American Cancer Society\u2019s Facts & Figures: 2020 Edition","volume":"11","author":"Viale","year":"2020","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_7","unstructured":"Mukkamalla, S.K.R., and Koya, S. (2025). Metastatic Melanoma. StatPearls, StatPearls Publishing."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1056\/NEJMoa1613210","article-title":"Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma","volume":"376","author":"Faries","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jmir.2019.05.001","article-title":"The Pathogenesis and Clinical Management of Cutaneous Melanoma: An Evidence-Based Review","volume":"50","author":"Burns","year":"2019","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.suc.2014.07.001","article-title":"Workup and staging of malignant melanoma","volume":"94","author":"Kauffmann","year":"2014","journal-title":"Surg. Clin. N. Am."},{"key":"ref_11","first-page":"472","article-title":"Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual","volume":"67","author":"Gershenwald","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.soc.2010.09.007","article-title":"Staging and prognosis of cutaneous melanoma","volume":"20","author":"Dickson","year":"2011","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"\u021a\u0103poi, D.A., Gheorghi\u0219an-G\u0103l\u0103\u021beanu, A.-A., Dumitru, A.V., Ciongariu, A.M., Furtunescu, A.R., Marin, A., and Costache, M. (2023). Primary Undifferentiated\/Dedifferentiated Cutaneous Melanomas\u2014A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24129985"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"989","DOI":"10.3390\/cancers2020989","article-title":"Prognostic significance of melanoma differentiation and trans-differentiation","volume":"2","author":"Maddodi","year":"2010","journal-title":"Cancers"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0168-9525(99)01955-1","article-title":"Pairing SOX off: With partners in the regulation of embryonic development","volume":"16","author":"Kamachi","year":"2000","journal-title":"Trends Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1534-5807(02)00223-X","article-title":"Twenty pairs of sox: Extent, homology, and nomenclature of the mouse and human sox transcription factor gene families","volume":"3","author":"Schepers","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1093\/nar\/27.6.1409","article-title":"From head to toes: The multiple facets of Sox proteins","volume":"27","author":"Wegner","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Schock, E.N., and LaBonne, C. (2020). Sorting Sox: Diverse Roles for Sox Transcription Factors During Neural Crest and Craniofacial Development. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.606889"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5709","DOI":"10.1158\/0008-5472.CAN-12-4620","article-title":"SOX10 ablation arrests cell cycle, induces senescence, and suppresses melanomagenesis","volume":"73","author":"Cronin","year":"2013","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1755-148X.2009.00578.x","article-title":"Frequent mutations in the MITF pathway in melanoma","volume":"22","author":"Cronin","year":"2009","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/ced.12928","article-title":"Expression of SOX10, ABCB5 and CD271 in melanocytic lesions and correlation with survival data of patients with melanoma","volume":"41","author":"Gambichler","year":"2016","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1038\/modpathol.2013.244","article-title":"Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma","volume":"27","author":"Hemminger","year":"2014","journal-title":"Mod. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"45352","DOI":"10.18632\/oncotarget.9977","article-title":"PRAME expression and promoter hypomethylation in epithelial ovarian cancer","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1016\/j.jtho.2016.08.120","article-title":"Safety and Immunogenicity of the PRAME Cancer Immunotherapeutic in Patients with Resected Non-Small Cell Lung Cancer: A Phase I Dose Escalation Study","volume":"11","author":"Pujol","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"629","DOI":"10.2217\/bmm.12.65","article-title":"The cancer testis antigen PRAME as a biomarker for solid tumor cancer management","volume":"6","author":"Goodison","year":"2012","journal-title":"Biomark. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e000068","DOI":"10.1136\/esmoopen-2016-000068","article-title":"Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: Results of a phase I dose escalation study","volume":"1","author":"Gutzmer","year":"2016","journal-title":"ESMO Open"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1001\/jamadermatol.2017.0473","article-title":"Utility of a Noninvasive 2-Gene Molecular Assay for Cutaneous Melanoma and Effect on the Decision to Biopsy","volume":"153","author":"Ferris","year":"2017","journal-title":"JAMA Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/cncr.30385","article-title":"An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi","volume":"123","author":"Clarke","year":"2017","journal-title":"Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ijc.2910310104","article-title":"Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation","volume":"31","author":"Gerdes","year":"1983","journal-title":"Int. J. Cancer."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.4049\/jimmunol.133.4.1710","article-title":"Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67","volume":"133","author":"Gerdes","year":"1984","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1093\/jnci\/djr393","article-title":"Assessment of Ki67 in breast cancer: Recommendations from the International Ki67 in Breast Cancer working group","volume":"103","author":"Dowsett","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_32","first-page":"10235","article-title":"Clinicopathological and prognostic significance of high Ki-67 labeling index in hepatocellular carcinoma patients: A meta-analysis","volume":"8","author":"Luo","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1136\/jclinpath-2015-203340","article-title":"The assessment of Ki-67 as a prognostic marker in neuroendocrine tumours: A systematic review and meta-analysis","volume":"69","author":"Ewings","year":"2016","journal-title":"J. Clin. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/path.1007","article-title":"Cyclin A expression in superficial spreading malignant melanomas correlates with clinical outcome","volume":"195","author":"Maelandsmo","year":"2001","journal-title":"J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, Q., Peng, Z., Shen, L., and Shen, L. (2021). Prognostic and Clinicopathological Value of Ki-67 in Melanoma: A Meta-Analysis. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.737760"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/DAD.0000000000002863","article-title":"The Utility of PRAME and Ki-67 as Prognostic Markers for Cutaneous Melanoma","volume":"47","author":"Asato","year":"2025","journal-title":"Am. J. Dermatopathol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ming, Z., Lim, S.Y., and Rizos, H. (2020). Genetic Alterations in the INK4a\/ARF Locus: Effects on Melanoma Development and Progression. Biomolecules, 10.","DOI":"10.3390\/biom10101447"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ricci, C., Dika, E., Ambrosi, F., Lambertini, M., Veronesi, G., and Barbara, C. (2022). Cutaneous Melanomas: A Single Center Experience on the Usage of Immunohistochemistry Applied for the Diagnosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115911"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"625","DOI":"10.21873\/anticanres.17450","article-title":"Cyclin E Expression and p16 Loss Are Strong Prognostic Biomarkers in Primary Invasive Cutaneous Melanoma","volume":"45","author":"Gkionis","year":"2025","journal-title":"Anticancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"815","DOI":"10.5858\/arpa.2017-0435-RA","article-title":"Immunohistochemical Expression of p16 in Melanocytic Lesions: An Updated Review and Meta-analysis","volume":"142","author":"Koh","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"154564","DOI":"10.1016\/j.prp.2023.154564","article-title":"\u201cParadoxical\u201d p16 overexpression in cutaneous melanoma: Molecular and immunohistochemical analysis of a rare phenomenon with a focus on cell cycle regulatory molecules","volume":"247","author":"Ricci","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_42","unstructured":"Elder, D.E., and Barnhill, R.Y. (2023). Chapter III: Melanocytic neoplasms. WHO Classification of Tumours Editorial Board. Skin Tumours, International Agency for Research on Cancer. [5th ed.]. Available online: https:\/\/tumourclassification.iarc.who.int\/chapters\/64."},{"key":"ref_43","unstructured":"Gershenwald, J.E., Scolyer, R.A., Hess, K.R., Thompson, J.F., Long, G.V., Ross, M.I., Lazar, A.J., Atkins, M.B., Balch, C.M., and Barnhill, R.L. (2017). Melanoma of the Skin. AJCC Cancer Staging Manual, Springer International Publishing. [8th ed.]."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"687","DOI":"10.14744\/nci.2022.57255","article-title":"Demographic and clinical features of cutaneous malignant melanoma patients: A single center cohort study","volume":"10","author":"Semiz","year":"2023","journal-title":"North. Clin. Istanb."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jaad.2018.07.041","article-title":"Cutaneous malignant melanoma incidence and mortality trends in Canada: A comprehensive population-based study","volume":"80","author":"Ghazawi","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/jdv.18635","article-title":"Patient presentation, skin biopsy utilization and cutaneous malignant melanoma incidence and mortality in northern Italy: Trends and correlations","volume":"37","author":"Bucchi","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e14131","DOI":"10.1111\/dth.14131","article-title":"Gender differences in cutaneous melanoma: Demographics, prognostic factors, and survival outcomes","volume":"33","author":"Behbahani","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1016\/j.bjps.2022.04.093","article-title":"Location of cutaneous malignant melanoma in Sweden 2004\u20132018\u2014Mortality and sex differences","volume":"75","author":"Zommorodi","year":"2022","journal-title":"J. Plast. Reconstr. Aesthet. Surg."},{"key":"ref_50","first-page":"444","article-title":"Impact of gender and primary tumor location on outcome of patients with cutaneous melanoma","volume":"9","author":"Voinea","year":"2016","journal-title":"J. Med. Life"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.abd.2022.06.006","article-title":"Epidemiology of cutaneous melanoma in Blumenau, Santa Catarina state, Brazil from 1980 to 2019","volume":"98","author":"Nasser","year":"2023","journal-title":"Bras. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/ijd.16559","article-title":"Trends in three major histological subtypes of cutaneous melanoma in the Netherlands between 1989 and 2016","volume":"62","author":"Otten","year":"2023","journal-title":"Int. J. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/bjd.21274","article-title":"Does the morphology of cutaneous melanoma help to explain the international differences in survival? Results from 1\u00a0578\u00a0482 adults diagnosed during 2000\u20132014 in 59 countries (CONCORD-3)","volume":"187","author":"Stiller","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_54","unstructured":"National Comprehensive Cancer Network (2025). Cutaneous Melanoma (Version 2.2025). NCCN Clinical Practice Guidelines in Oncology, National Comprehensive Cancer Network. Available online: https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1492."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jaad.2018.08.055","article-title":"Guidelines of care for the management of primary cutaneous melanoma","volume":"80","author":"Swetter","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1001\/jamadermatol.2023.0127","article-title":"Early detection and prognostic assessment of cutaneous melanoma: Consensus on optimal practice and the role of gene expression profile testing","volume":"159","author":"Leachman","year":"2023","journal-title":"JAMA Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1245\/s10434-024-16379-2","article-title":"Society of Surgical Oncology consensus statement: Assessing the evidence for and utility of gene expression profiling of primary cutaneous melanoma","volume":"32","author":"Bartlett","year":"2025","journal-title":"Ann. Surg. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Mokos, M., Prka\u010din, I., Ga\u0107ina, K., Brki\u0107, A., Pondeljak, N., and \u0160itum, M. (2025). Therapeutic Opportunities in Melanoma Through PRAME Expression. Biomedicines, 13.","DOI":"10.3390\/biomedicines13081988"},{"key":"ref_59","first-page":"A1009","article-title":"Safety and anti-tumour activity of TCR-engineered autologous, PRAME-directed T cells across multiple advanced solid cancers at low doses\u2014Clinical update on the ACTengine\u00ae IMA203 trial","volume":"9","author":"Wermke","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S0140-6736(23)02268-7","article-title":"Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): A randomised, phase 2b study","volume":"403","author":"Weber","year":"2024","journal-title":"Lancet"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/cup.14495","article-title":"PRAME expression in cutaneous melanoma does not correlate with disease-specific survival","volume":"50","author":"Parra","year":"2023","journal-title":"J. Cutan. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ronchi, A., Cazzato, G., Ingravallo, G., D\u2019Abbronzo, G., Argenziano, G., Moscarella, E., Brancaccio, G., and Franco, R. (2024). PRAME Is an Effective Tool for the Diagnosis of Nevus-Associated Cutaneous Melanoma. Cancers, 16.","DOI":"10.3390\/cancers16020278"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Blount, S.L., Liu, X., and McBride, J.D. (2024). The Utilization of PRAME in the Diagnosis, Prognosis, and Treatment of Melanoma. Cells, 13.","DOI":"10.20944\/preprints202409.1316.v1"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Tapoi, D.A., Gheorghi\u0219an-G\u0103l\u0103\u021beanu, A.-A., Gosman, L.M., Derewicz, D., and Costache, M. (2024). The Prognostic Value of Proliferative Activity in Cutaneous Melanoma: A Pilot Study Evaluating the Mitotic Rate and Ki67 Index to Predict Patient Outcomes. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061318"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1097\/COC.0000000000000604","article-title":"Prognosis and Management of Thick and Ultrathick Melanoma","volume":"42","author":"Blakely","year":"2019","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.surg.2018.04.016","article-title":"Tumor mitotic rate is an independent predictor of survival for nonmetastatic melanoma","volume":"164","author":"Evans","year":"2018","journal-title":"Surgery"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Buja, A., Rugge, M., Cozzolino, C., Dossi, F., Zorzi, M., Vecchiato, A., de Luca, G., Del Fiore, P., Tropea, S., and dall\u2019Olmo, L. (2024). Could the mitotic count improve personalized prognosis in melanoma patients?. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0302309"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1177\/1066896921995985","article-title":"The Relationship Between Epidermal Mitotic Density, Atypical Mitotic Figure Density, Breslow Depth, Ulceration, and Dermal Mitotic Rate in Cutaneous Melanoma: A Retrospective Cohort Study","volume":"29","author":"Marsch","year":"2021","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_69","first-page":"800","article-title":"Immunohistochemical analysis of Bcl-2, nuclear S100A4, MITF, and Ki67 for risk stratification of early-stage melanoma\u2014A combined IHC score for melanoma risk stratification","volume":"17","author":"Jurmeister","year":"2019","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/jso.25111","article-title":"Association between Ki-67 expression and clinical outcomes among patients with clinically node-negative, thick primary melanoma who underwent nodal staging","volume":"118","author":"Robinson","year":"2018","journal-title":"J. Surg. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1007\/s12094-017-1774-3","article-title":"Ki67 targeted strategies for cancer therapy","volume":"20","author":"Yang","year":"2018","journal-title":"Clin. Transl. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.jgo.2018.01.001","article-title":"Melanoma in the very elderly: Management in patients 85 years of age and over","volume":"9","author":"Rees","year":"2018","journal-title":"J. Geriatr. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S349","DOI":"10.4103\/jcrt.jcrt_815_21","article-title":"Cutaneous melanoma survival rates of the elderly are not worse than those of the young, yet they have some specific differences","volume":"19","author":"Ferhatoglu","year":"2023","journal-title":"J. Cancer Res. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"\u021a\u0103poi, D.A., Derewicz, D., Gheorghi\u0219an-G\u0103l\u0103\u021beanu, A.-A., Dumitru, A.V., Ciongariu, A.M., and Costache, M. (2023). The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102616"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e513","DOI":"10.1111\/jdv.16423","article-title":"Age as a prognostic factor in thick and ultrathick melanomas without lymph node metastasis","volume":"34","author":"Boada","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1136\/jclinpath-2013-202127","article-title":"Immunohistochemical analysis of molecular drivers in melanoma identifies p16 as an independent prognostic biomarker","volume":"67","author":"Guldberg","year":"2014","journal-title":"J. Clin. Pathol."},{"key":"ref_77","first-page":"1628247","article-title":"Immunohistochemical Analysis of BRAF (V600E) Mutation and P16 Expression in Malignant Melanoma in Lagos, Nigeria: A 10-Year Retrospective Study","volume":"2019","author":"Obadofin","year":"2019","journal-title":"J. Ski. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1177\/229255031101900313","article-title":"P16 protein expression in primary cutaneous melanoma with positive and negative lymph node biopsies: Particular aspects of a study performed at the Hospital de Clinicas de Porto Alegre, Brazil","volume":"19","author":"Fauri","year":"2011","journal-title":"Can. J. Plast. Surg."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.humpath.2003.08.017","article-title":"Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients","volume":"35","author":"Ghiorzo","year":"2004","journal-title":"Hum. Pathol."},{"key":"ref_80","first-page":"1845","article-title":"Loss of nuclear p16 protein expression correlates with increased tumor cell proliferation (Ki-67) and poor prognosis in patients with vertical growth phase melanoma","volume":"6","author":"Straume","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1600-0560.2008.01154.x","article-title":"p16 expression differentiates between desmoplastic Spitz nevus and desmoplastic melanoma","volume":"36","author":"Hilliard","year":"2009","journal-title":"J. Cutan. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1097\/00008390-200212000-00003","article-title":"Loss of p16 expression is associated with histological features of melanoma invasion","volume":"12","author":"Pavey","year":"2002","journal-title":"Melanoma Res."},{"key":"ref_83","first-page":"191","article-title":"Prognostic prediction of the immunohistochemical expression of p16 and p53 in cutaneous melanoma: A comparison of two populations from different geographical regions","volume":"50","author":"Sirigu","year":"2006","journal-title":"Eur. J. Histochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"77","DOI":"10.7555\/JBR.36.20210163","article-title":"Melanoma therapeutics: A literature review","volume":"36","author":"Dhanyamraju","year":"2022","journal-title":"J. Biomed. Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Soo, J.K., Castle, J.T., and Bennett, D.C. (2023). Preferential killing of melanoma cells by a p16-related peptide. Biol. Open., 12.","DOI":"10.1242\/bio.059965"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e006947","DOI":"10.1136\/jitc-2023-006947","article-title":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0","volume":"11","author":"Pavlick","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Fiorentino, V., Pizzimenti, C., Franchina, M., Pepe, L., Russotto, F., Tralongo, P., Micali, M.G., Militi, G.B., and Lentini, M. (2024). Programmed Cell Death Ligand 1 Immunohistochemical Expression and Cutaneous Melanoma: A Controversial Relationship. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010676"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s00384-022-04119-5","article-title":"The impact of low serum cholinesterase levels on survival in patients with colorectal cancer","volume":"37","author":"Takano","year":"2022","journal-title":"Int. J. Color. Dis."},{"key":"ref_89","first-page":"654","article-title":"Butyrylcholinesterase in UV reactions","volume":"64","author":"Nicolae","year":"2013","journal-title":"Rev. Chim."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1021\/acs.analchem.4c06407","article-title":"NIR fluorescence strategy for the early diagnosis of melanoma liver metastasis based on the cascade reaction of two specific bioenzymes","volume":"97","author":"Zhang","year":"2025","journal-title":"Anal. Chem."},{"key":"ref_91","unstructured":"Cancer Genome Atlas Network (2015). Genomic classification of cutaneous melanoma. Cell, 161, 1681\u20131696."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1733\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:58:21Z","timestamp":1759147101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":91,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["medicina61101733"],"URL":"https:\/\/doi.org\/10.3390\/medicina61101733","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}