{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:40:37Z","timestamp":1762080037501,"version":"build-2065373602"},"reference-count":81,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cutaneous melanoma is a severe neoplasm that shows early invasiveness of the lymph nodes draining the primary site, with increased risk of distant metastases and recurrence. The tissue biomarker identification could be a new frontier to predict the risk of early lymph node invasiveness, especially in cases considered by current guidelines to be at low risk of lymph node involvement and not requiring evaluation of the sentinel lymph node (SLN). For this reason, we present a narrative review of the literature, seeking to provide an overview of current tissue biomarkers, particularly vascular endothelium growth factors (VEGF), Tetraspanin CD9, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), D2-40, and gene expression profile test (31-GEP). Among these, 31-GEP seems to be able to provide a distinction between low or high risk for positive SLN classes. VEGF receptor-3 and CD9 expression may be independent predictors of positive SLN. Lastly, LYVE-1 and D2-40 allow an easier assessment of lymph vascular invasion, which can be considered a good predictor of SLN status. In conclusion, biomarkers to assess the lymph node status of cutaneous melanoma patients may play an important role in those cases where the clinician is in doubt whether or not to perform SLN biopsy.<\/jats:p>","DOI":"10.3390\/ijms24010144","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T01:33:12Z","timestamp":1671672792000},"page":"144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Tissue Biomarkers Predicting Lymph Node Status in Cutaneous Melanoma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0091-4067","authenticated-orcid":false,"given":"Giulio","family":"Rizzetto","sequence":"first","affiliation":[{"name":"Clinic of Dermatology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-5620","authenticated-orcid":false,"given":"Guendalina","family":"Lucarini","sequence":"additional","affiliation":[{"name":"Histology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edoardo","family":"De Simoni","sequence":"additional","affiliation":[{"name":"Clinic of Dermatology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Molinelli","sequence":"additional","affiliation":[{"name":"Clinic of Dermatology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2087-2776","authenticated-orcid":false,"given":"Monica","family":"Mattioli-Belmonte","sequence":"additional","affiliation":[{"name":"Histology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Offidani","sequence":"additional","affiliation":[{"name":"Clinic of Dermatology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oriana","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Clinic of Dermatology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Strashilov, S., and Yordanov, A. (2021). Aetiology and Pathogenesis of Cutaneous Melanoma: Current Concepts and Advances. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126395"},{"key":"ref_2","first-page":"2113","article-title":"Clinical and prognostic significance of survivin, AKT and VEGF in primary mucosal oral melanoma","volume":"35","author":"Simonetti","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1111\/odi.12048","article-title":"Microvessel density and VEGF, HIF-1\u03b1 expression in primary oral melanoma: Correlation with prognosis","volume":"19","author":"Simonetti","year":"2012","journal-title":"Oral Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1056\/NEJMsb2019760","article-title":"The Rapid Rise in Cutaneous Melanoma Diagnoses","volume":"384","author":"Welch","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ejca.2019.11.014","article-title":"European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics\u2014Update 2019","volume":"126","author":"Garbe","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1002\/ijc.33479","article-title":"Skin melanoma deaths within 1 or 3 years from diagnosis in Europe","volume":"148","author":"Sacchetto","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.det.2018.12.005","article-title":"What\u2019s New in Melanoma","volume":"37","author":"Prado","year":"2019","journal-title":"Dermatol. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/CMR.0000000000000674","article-title":"Vascular endothelial growth factor\/semaphorin-3A ratio and SEMA3A expression in cutaneous malignant melanoma","volume":"30","author":"Lucarini","year":"2020","journal-title":"Melanoma Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1177\/039463200702000212","article-title":"In Melanoma Changes of Immature and Mature Dendritic Cell Expression Correlate with Tumor Thickness: An Immunohistochemical Study","volume":"20","author":"Simonetti","year":"2007","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e000832","DOI":"10.1136\/jitc-2020-000832","article-title":"Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy","volume":"9","author":"Prokopi","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s13046-021-01926-6","article-title":"Hypoxia-dependent drivers of melanoma progression","volume":"40","author":"Mallone","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1684\/ejd.2016.2787","article-title":"Genetic epidemiology of melanoma","volume":"26","author":"Ribero","year":"2016","journal-title":"Eur. J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1111\/j.0022-202X.2005.23882.x","article-title":"Role of Tetraspanins CD9 and CD151 in Primary Melanocyte Motility","volume":"125","author":"Barreiro","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"364","DOI":"10.6004\/jnccn.2021.0018","article-title":"NCCN Guidelines\u00ae Insights: Melanoma: Cutaneous, Version 2.2021","volume":"19","author":"Swetter","year":"2021","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_16","unstructured":"(2022, October 22). AIOM Guidelines. Available online: https:\/\/snlg.iss.it\/wp-content\/uploads\/2021\/10\/LG-127_Melanoma_agg2021.pdf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1200\/JCO.2005.03.2342","article-title":"Prospective Multi-Institutional Study of Reverse Transcriptase Polymerase Chain Reaction for Molecular Staging of Melanoma","volume":"24","author":"Scoggins","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10555-006-9026-y","article-title":"Lymphatic endothelial cells, tumor lymphangiogenesis and metastasis: New insights into intratumoral and peritumoral lymphatics","volume":"25","author":"Ji","year":"2006","journal-title":"Cancer Metastasis Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.humpath.2007.10.017","article-title":"Lymphatic invasion revealed by multispectral imaging is common in primary melanomas and associates with prognosis","volume":"39","author":"Xu","year":"2008","journal-title":"Hum. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1111\/j.1600-0560.2008.01242.x","article-title":"Immunohistochemical detection of lymphovascular invasion with D2-40 in melanoma correlates with sentinel lymph node status, metastasis and survival","volume":"36","author":"Petersson","year":"2009","journal-title":"J. Cutan. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.jaad.2009.04.026","article-title":"Lymphatic invasion detected by D2-40\/S-100 dual immunohistochemistry does not predict sentinel lymph node status in melanoma","volume":"61","author":"Petitt","year":"2009","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1097\/PAS.0b013e31822573f5","article-title":"Clinical Relevance of Detection of Lymphovascular Invasion in Primary Melanoma Using Endothelial Markers D2-40 and CD34","volume":"35","author":"Rose","year":"2011","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1016\/S0002-9440(10)64328-3","article-title":"Tumor lymphangiogenesis: A novel prognostic indicator for cutaneous melanoma metastasis and survival","volume":"162","author":"Dadras","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/ijc.25795","article-title":"Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx","volume":"129","author":"Huber","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kilvaer, T.K., Valkov, A., Sorbye, S., Smeland, E., Bremnes, R.M., Busund, L.-T., and Donnem, T. (2010). Profiling of VEGFs and VEGFRs as Prognostic Factors in Soft Tissue Sarcoma: VEGFR-3 Is an Independent Predictor of Poor Prognosis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015368"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/ar.20736","article-title":"Lymphangiogenesis and Its Relationship With Lymphatic Metastasis and Prognosis in Malignant Melanoma","volume":"291","author":"Liu","year":"2008","journal-title":"Anat. Rec."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"372979","DOI":"10.1155\/2014\/372979","article-title":"Lymphangiogenesis and Its Correlation with the VEGF Expression and the Sentinel Lymph Node in Cutaneous Melanomas","volume":"2014","author":"Buzrla","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_28","first-page":"483439","article-title":"Multiple Roles for VEGF in Non-Melanoma Skin Cancer: Angiogenesis and Beyond","volume":"2012","author":"Johnson","year":"2012","journal-title":"J. Ski. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00428-011-1044-7","article-title":"Stromal expression of vascular endo- thelial growth factor C is relevant to predict sentinel lymph node status in melanomas","volume":"458","author":"Gallego","year":"2011","journal-title":"Virchows Arch."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00428-008-0641-6","article-title":"The role of VEGF-C staining in predicting regional metastasis in melanoma","volume":"453","author":"Boone","year":"2008","journal-title":"Virchows Arch."},{"key":"ref_31","first-page":"273","article-title":"The role of vascular endothelial growth factors and their receptors in malignant melanomas","volume":"55","author":"Brychtova","year":"2008","journal-title":"Neoplasma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/modpathol.3800410","article-title":"Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes","volume":"18","author":"Dadras","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"adv00235","DOI":"10.2340\/00015555-3588","article-title":"Vascular Endothelial Growth Factor Receptor-3 Expression Predicts Sentinel Node Status in Primary Cutaneous Melanoma","volume":"100","author":"Toberer","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrc3640","article-title":"Tetraspanin proteins promote multiple cancer stages","volume":"14","author":"Hemler","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/mc.20580","article-title":"Expression and function of CD9 in melanoma cells","volume":"49","author":"Fan","year":"2009","journal-title":"Mol. Carcinog."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1042\/BST0390563","article-title":"Tetraspanin CD9 in cell migration","volume":"39","author":"Powner","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lucarini, G., Molinelli, E., Licini, C., Rizzetto, G., Radi, G., Goteri, G., Mattioli-Belmonte, M., Offidani, A., and Simonetti, O. (2022). Tetraspanin CD9 Expression Predicts Sentinel Node Status in Patients with Cutaneous Melanoma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094775"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3233\/CBM-170422","article-title":"CD9 expression indicates a poor outcome in acute lymphoblastic leukemia","volume":"21","author":"Liang","year":"2018","journal-title":"Cancer Biomark."},{"key":"ref_39","first-page":"3054","article-title":"Overexpression of CD9 correlates with tumor stage and lymph node metastasis in esophageal squamous cell carcinoma","volume":"8","author":"Huan","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_40","first-page":"493","article-title":"Prognostic value of NF-\u03baB, CD9, and VEGF in gastrointestinal stromal tumors","volume":"17","author":"Tasdemir","year":"2013","journal-title":"Contemp. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/bjc.2017.487","article-title":"CD9-positive exosomes from cancer-associated fibroblasts stimulate the migration ability of scirrhous-type gastric cancer cells","volume":"118","author":"Miki","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_42","first-page":"5525","article-title":"Tetraspanin CD9 interacts with \u03b1-secretase to enhance its oncogenic function in pancreatic cancer","volume":"12","author":"Lu","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"112009","DOI":"10.1016\/j.yexcr.2020.112009","article-title":"ALDH1A1+ ovarian cancer stem cells co-expressing surface markers CD24, EPHA1 and CD9 form tumours in vivo","volume":"392","author":"Nagare","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/bs.mie.2020.06.011","article-title":"Immunocapture-based ELISA to characterize and quantify exosomes in both cell culture supernatants and body fluids","volume":"645","author":"Logozzi","year":"2020","journal-title":"Methods Enzymol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1182\/blood.V98.13.3717","article-title":"Regulatory role of tetraspanin CD9 in tumor\u2013endothelial cell interaction during transendothelial invasion of melanoma cells","volume":"98","author":"Longo","year":"2001","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1097\/01.MP.0000089777.58000.B2","article-title":"CD9 Expression on Lymphatic Vessels in Head and Neck Mucosa","volume":"16","author":"Erovic","year":"2003","journal-title":"Mod. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/j.1600-0560.2008.01166.x","article-title":"Lymphatic invasion in cutaneous melanoma is associated with sentinel lymph node metastasis","volume":"36","author":"Doeden","year":"2009","journal-title":"J. Cutan. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jaad.2010.03.005","article-title":"D2-40 lymphatic marker for detecting lymphatic invasion in thin to intermediate thickness melanomas: Association with sentinel lymph node status and prognostic value\u2014A retrospective case study","volume":"64","author":"Fohn","year":"2011","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.jaad.2015.01.009","article-title":"Gene expression profiling for molecular staging of cutaneous melanoma in patients undergoing sentinel lymph node biopsy","volume":"72","author":"Gerami","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13000-018-0690-3","article-title":"Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients","volume":"13","author":"Cook","year":"2018","journal-title":"Diagn. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1002\/cam4.2128","article-title":"Prospective validation of the prognostic 31-gene expression profiling test in primary cutaneous melanoma","volume":"8","author":"Keller","year":"2019","journal-title":"Cancer Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/jdv.15454","article-title":"Early outcome of a 31-gene expression profile test in 86 AJCC stage IB\u2013II melanoma patients. A prospective multicentre cohort study","volume":"33","author":"Podlipnik","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1097\/DSS.0000000000001588","article-title":"Estimation of Prognosis in Invasive Cutaneous Melanoma: An Independent Study of the Accuracy of a Gene Expression Profile Test","volume":"44","author":"Greenhaw","year":"2018","journal-title":"Dermatol. Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13045-017-0520-1","article-title":"Interim analysis of survival in a prospective, multi-center registry cohort of cutaneous melanoma tested with a prognostic 31-gene expression profile test","volume":"10","author":"Hsueh","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.2217\/fon-2018-0912","article-title":"Guidance of sentinel lymph node biopsy decisions in patients with T1\u2013T2 melanoma using gene expression profiling","volume":"15","author":"Vetto","year":"2019","journal-title":"Futur. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jaad.2018.07.028","article-title":"Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria","volume":"80","author":"Gastman","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10585-021-10089-9","article-title":"Sentinel lymph node biopsy in melanoma: Beyond histologic factors","volume":"39","author":"Carr","year":"2021","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/ng0298-171","article-title":"SOX10 mutations in patients with Waardenburg-Hirschsprung disease","volume":"18","author":"Pingault","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/S0014-5793(03)01446-7","article-title":"Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors","volume":"556","author":"Ludwig","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1111\/j.1600-0560.2010.01568.x","article-title":"SOX10 immunostaining distinguishes desmoplastic melanoma from excision scar","volume":"37","author":"Karamchandani","year":"2010","journal-title":"J. Cutan. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1365-2559.2009.03415.x","article-title":"Diagnostic value of Sox10 immunohistochemical staining for the detection of metastatic melanoma in sentinel lymph nodes","volume":"55","author":"Blochin","year":"2009","journal-title":"Histopathology"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Manninen, A., Gardberg, M., Juteau, S., Ilmonen, S., Jukonen, J., Andersson, N., and Carp\u00e9n, O. (2019). BRAF immunohistochemistry predicts sentinel lymph node involvement in intermediate thickness melanomas. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0216043"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/modpathol.2017.104","article-title":"Molecular testing for BRAF mutations to inform melanoma treatment decisions: A move toward precision medicine","volume":"31","author":"Cheng","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.1245\/s10434-016-5137-z","article-title":"Sentinel Lymph Node Biopsy in Thin Cutaneous Melanoma: A Systematic Review and Meta-Analysis","volume":"23","author":"Cordeiro","year":"2016","journal-title":"Ann. Surg. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1002\/cam4.2358","article-title":"Survival analysis and sentinel lymph node status in thin cutaneous melanoma: A multicenter observational study","volume":"8","author":"Ribero","year":"2019","journal-title":"Cancer Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1245\/s10434-018-6348-2","article-title":"Predictors for Use of Sentinel Node Biopsy and the Association with Improved Survival in Melanoma Patients Who Have Nodal Staging","volume":"25","author":"Murtha","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3548","DOI":"10.1158\/1078-0432.CCR-09-2797","article-title":"Vascular Endothelial Growth Factor Receptors VEGFR-2 and VEGFR-3 Are Localized Primarily to the Vasculature in Human Primary Solid Cancers","volume":"16","author":"Smith","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.humpath.2009.08.016","article-title":"Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays","volume":"41","author":"Mehnert","year":"2010","journal-title":"Hum. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1097\/SLA.0b013e3182306c72","article-title":"Sentinel Lymph Node Biopsy in Patients With Thin Primary Cutaneous Melanoma","volume":"255","author":"Murali","year":"2012","journal-title":"Ann. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"501","DOI":"10.5301\/tj.5000298","article-title":"Evaluation of Melanoma Features and Their Relationship with Nodal Disease: The Importance of the Pathological Report","volume":"101","author":"Bertolli","year":"2015","journal-title":"Tumori J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1245\/s10434-019-07690-4","article-title":"Age and Lymphovascular Invasion Accurately Predict Sentinel Lymph Node Metastasis in T2 Melanoma Patients","volume":"26","author":"Egger","year":"2019","journal-title":"Ann. Surg. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/cam4.1320","article-title":"Clinical impact of ulceration width, lymphovascular invasion, microscopic satellitosis, perineural invasion, and mitotic rate in patients undergoing sentinel lymph node biopsy for cutaneous melanoma: A retrospective observational study at a comprehensive","volume":"7","author":"Namikawa","year":"2018","journal-title":"Cancer Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1245\/s10434-013-3388-5","article-title":"Prognosis of patients with melanoma and microsatellitosis undergoing sentinel lymph node biopsy","volume":"21","author":"Bartlett","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1177\/000313481107700819","article-title":"Regression Does Not Predict Nodal Metastasis or Survival in Patients with Cutaneous Melanoma","volume":"77","author":"Burton","year":"2011","journal-title":"Am. Surg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1245\/s10434-013-3464-x","article-title":"Age as a Predictor of Sentinel Node Metastasis among Patients with Localized Melanoma: An Inverse Correlation of Melanoma Mortality and Incidence of Sentinel Node Metastasis Among Young and Old Patients","volume":"21","author":"Balch","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"433","DOI":"10.4081\/oncol.2019.433","article-title":"Evolving management of positive regional lymph nodes in melanoma: Past, present and future directions","volume":"13","author":"Fayne","year":"2019","journal-title":"Oncol. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1080\/03007995.2022.2033560","article-title":"Expanded evidence that the 31-gene expression profile test provides clinical utility for melanoma management in a multicenter study","volume":"38","author":"Dillon","year":"2022","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e12197","DOI":"10.1002\/jev2.12197","article-title":"Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes","volume":"11","author":"Leary","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e1667742","DOI":"10.1080\/2162402X.2019.1667742","article-title":"Identification of novel, immune-mediating extracellular vesicles in human lymphatic effluent draining primary cutaneous melanoma","volume":"8","author":"Maus","year":"2019","journal-title":"OncoImmunology"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Surman, M., St\u0119pie\u0144, E., and Przyby\u0142o, M. (2019). Melanoma-Derived Extracellular Vesicles: Focus on Their Proteome. Proteomes, 7.","DOI":"10.3390\/proteomes7020021"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"109320","DOI":"10.1016\/j.intimp.2022.109320","article-title":"Melanoma-derived exosomes: Versatile extracellular vesicles for diagnosis, metastasis, immune modulation, and treatment of melanoma","volume":"113","author":"Moosavian","year":"2022","journal-title":"Int. Immunopharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/144\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:47:03Z","timestamp":1760147223000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/1\/144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,21]]},"references-count":81,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24010144"],"URL":"https:\/\/doi.org\/10.3390\/ijms24010144","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,12,21]]}}}