{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:56:15Z","timestamp":1792418175338,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:00:00Z","timestamp":1688947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immunohistochemistry\u2010based protein biomarkers can provide useful prognostic information in cutaneous melanoma. The independent prognostic value of Ki\u201067 has been studied with variable results. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a useful new ancillary tool for distinguishing cutaneous nevi from melanoma; however, its prognostic value has not been well studied. We evaluated PRAME as a prognostic marker in cutaneous melanoma, compared to Ki\u201067.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the immunohistochemical expression of PRAME and Ki\u201067 in 165 melanocytic lesions, including 92 primary melanomas, 19 metastatic melanomas, and 54 melanocytic nevi using tissue microarrays. PRAME immunostaining was scored based on the percentage of positive nuclei: 0 &lt;1%, 1+ 1%\u201325%, 2+ 26%\u201350%, 3+ 51%\u201375%, and 4+ &gt;75%. The percentage of Ki\u201067\u2010positive tumor nuclei was used to calculate the proliferation index.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PRAME and Ki\u201067 both showed significantly increased expression in melanomas compared to nevi (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001 and <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, respectively). There was no significant difference in PRAME expression in primary versus metastatic melanomas. By contrast, the Ki\u201067 proliferation index was higher in metastatic melanoma than in primary melanoma (<jats:italic>p<\/jats:italic>\u2009=\u20090.013). Increased Ki\u201067 index correlated with ulceration (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), increased Breslow depth (<jats:italic>p<\/jats:italic>\u2009=\u20090.001), and higher mitotic rate (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), whereas increased PRAME expression correlated with higher mitotic rate (<jats:italic>p<\/jats:italic>\u2009=\u20090.047) and Ki\u201067 index (<jats:italic>p<\/jats:italic>\u2009=\u20090.007). Increased Ki\u201067 index correlated with worse disease\u2010specific survival in patients with primary melanoma (<jats:italic>p<\/jats:italic> &lt; 0.001), but PRAME expression did not show prognostic significance in disease\u2010specific survival (<jats:italic>p<\/jats:italic> = 0.63). In a multivariable analysis of patients with primary melanoma, tumor Breslow depth, ulceration, mitotic rate, and Ki\u201067 index were each independent predictors of disease\u2010specific survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.006, 0.02, 0.001, and 0.04, respectively); however, PRAME expression was not predictive of disease\u2010specific survival (<jats:italic>p<\/jats:italic>\u2009=\u20090.64).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Ki\u201067 is an independent prognostic marker; although increased PRAME expression correlates with the Ki\u201067 proliferation index and mitotic rate, PRAME is not an independent prognostic marker for cutaneous melanoma. PRAME and Ki\u201067 are useful ancillary tools for distinguishing benign from malignant melanocytic lesions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cup.14495","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T04:01:18Z","timestamp":1689048078000},"page":"903-912","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>PRAME<\/scp> expression in cutaneous melanoma does not correlate with disease\u2010specific survival"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7378-5214","authenticated-orcid":false,"given":"Ourania","family":"Parra","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Hanover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Hanover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongze","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, SABER, School of Public Health University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan N.","family":"Coffing","sequence":"additional","affiliation":[{"name":"Metropolitan Pathologists  Lakewood Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9462-652X","authenticated-orcid":false,"given":"Konstantinos","family":"Linos","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-0381","authenticated-orcid":false,"given":"Robert E.","family":"LeBlanc","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Hanover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8403-7585","authenticated-orcid":false,"given":"Shabnam","family":"Momtahen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Hanover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravindhan","family":"Sriharan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Hanover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Cloutier","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Hanover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Hanover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9654-2100","authenticated-orcid":false,"given":"Shaofeng","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Dartmouth\u2010Hitchcock Medical Center  Lebanon New Hampshire USA"},{"name":"Geisel School of Medicine at Dartmouth  Hanover New Hampshire USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1074\u20107613(00)80426\u20104"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001134"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.13876"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2017.0729"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9977"},{"issue":"18","key":"e_1_2_6_7_1","first-page":"4090","article-title":"Heterogeneous expression of the tumor\u2010associated antigens RAGE\u20101, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T\u2010cell\u2010based immunotherapies?","volume":"58","author":"Neumann E","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.11.005"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.08.120"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13569\u2010017\u20100077\u20103"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153864"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8828579"},{"issue":"2","key":"e_1_2_6_13_1","first-page":"185","article-title":"PRAME is a potential carcinogenic biomarker that correlates with patient prognosis and tumor immunity based on pan\u2010cancer analysis","volume":"52","author":"Zhao Q","year":"2022","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010019\u201007985\u20106"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.13799"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10962"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201015\u20102071"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379\u2010019\u20100335\u20104"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0165\u20104608(02)00582\u20104"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0165\u20104608(01)00570\u20102"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2001.29658"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000328518"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10685"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000012038"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.0735"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0190\u20109622(96)90607\u20106"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-10-140"},{"issue":"6","key":"e_1_2_6_28_1","first-page":"2871","article-title":"Diagnostic and prognostic value of ProEx C and GLUT1 in melanocytic lesions","volume":"36","author":"Yan S","year":"2016","journal-title":"Anticancer Res"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000626"},{"issue":"1","key":"e_1_2_6_30_1","first-page":"24","article-title":"Tissue microarray: a new technology for amplification of tissue resources","volume":"7","author":"Rimm DL","year":"2001","journal-title":"Cancer J"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000072747.08404.38"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102559.2003.01556.x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100560.1996.tb01307.x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100560.1991.tb01234.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.109282"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523\u20101747.ep12312431"}],"container-title":["Journal of Cutaneous Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cup.14495","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T08:26:19Z","timestamp":1694161579000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cup.14495"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,10]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1111\/cup.14495"],"URL":"https:\/\/doi.org\/10.1111\/cup.14495","archive":["Portico"],"relation":{},"ISSN":["0303-6987","1600-0560"],"issn-type":[{"value":"0303-6987","type":"print"},{"value":"1600-0560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,10]]},"assertion":[{"value":"2023-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}