{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:52:51Z","timestamp":1791975171473,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Uveal melanoma (UM) is the most common primary intra\u2010ocular malignancy in adults and carries a high risk of metastatic disease, affecting approximately 50% of patients despite advances in local tumour control. PRAME (PReferentially expressed Antigen in MElanoma) has emerged as a marker for metastatic risk; however, evidence is largely derived from mRNA expression studies rather than routine immunohistochemistry (IHC). This study evaluates PRAME protein expression by IHC in a large UM cohort and examines its association with clinicopathological features and survival outcomes. A total of 403 UM cases were included. PRAME IHC was performed on tissue microarrays (TMAs) and\/or whole tumour sections and scored as positive based on nuclear staining in &gt;10% of tumour cells. Associations were assessed using chi\u2010square and Mann\u2013Whitney\n                    <jats:italic>U<\/jats:italic>\n                    tests. Survival outcomes were analysed using Kaplan\u2013Meier curves and Cox proportional hazards models. PRAME positivity was identified in 5% of TMA cases and 40% of whole\u2010section cases. On TMAs, PRAME expression was associated with worse overall survival (median 26 versus 50\u2009months;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03) but not metastasis\u2010free survival (MFS). In contrast, whole\u2010section PRAME expression was strongly associated with shorter MFS (median 5 versus 20\u2009months;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and worse overall survival (median 13 versus 52\u2009months;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04). In multivariate analysis including age, American Joint Committee on Cancer stage and BAP1 status, whole\u2010section PRAME positivity remained an independent adverse predictor of MFS (hazard ratio =\u200910.5,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002). PRAME IHC is a clinically meaningful prognostic biomarker in UM, particularly when assessed on whole tumour sections, where it provides strong independent prognostic information.\n                  <\/jats:p>","DOI":"10.1002\/2056-4538.70116","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:28:52Z","timestamp":1791973732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PRAME<\/scp>\n                    predicting outcome in uveal melanoma"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-4154","authenticated-orcid":false,"given":"Sally","family":"Owens","sequence":"first","affiliation":[{"name":"Life Sciences Institute, School of Biotechnology Dublin City University  Dublin Ireland"},{"name":"National Ophthalmic Pathology Laboratory, Department of Pathology  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Walsh","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, School of Biotechnology Dublin City University  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Horgan","sequence":"additional","affiliation":[{"name":"Ocular Oncology Service, Department of Ophthalmology Research Foundation Royal Victoria Eye &amp; Ear Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Murtagh","sequence":"additional","affiliation":[{"name":"Ocular Oncology Service, Department of Ophthalmology Research Foundation Royal Victoria Eye &amp; Ear Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Hanratty","sequence":"additional","affiliation":[{"name":"National Ophthalmic Pathology Laboratory, Department of Pathology  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grainne","family":"Finegan","sequence":"additional","affiliation":[{"name":"National Ophthalmic Pathology Laboratory, Department of Pathology  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ivers","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, School of Biotechnology Dublin City University  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Crown","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, St. Vincent's University Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, School of Biotechnology Dublin City University  Dublin Ireland"},{"name":"National Ophthalmic Pathology Laboratory, Department of Pathology  Dublin Ireland"},{"name":"Ocular Oncology Service, Department of Ophthalmology Research Foundation Royal Victoria Eye &amp; Ear Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2147\/OPTH.S89591","article-title":"Uveal melanoma: epidemiology, etiology, and treatment of primary disease","volume":"11","author":"Krantz BA","year":"2017","journal-title":"Clin Ophthalmol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41389-024-00511-8","article-title":"PKC\u2010independent PI3K signalling diminishes PKC inhibitor sensitivity in uveal melanoma","volume":"13","author":"Park JJ","year":"2024","journal-title":"Oncogene"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","DOI":"10.1167\/iovs.64.13.45","article-title":"Worldwide incidence of ocular melanoma and correlation with pigmentation\u2010related risk factors","volume":"64","author":"Wu M","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.3892\/etm.2021.10863","article-title":"Uveal melanoma diagnosis and current treatment options (review)","volume":"22","author":"Branisteanu DC","year":"2021","journal-title":"Exp Ther Med"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1093\/annonc\/mdz176","article-title":"Meta\u2010analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study","volume":"30","author":"Khoja L","year":"2019","journal-title":"Ann Oncol"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10384-019-00656-9","article-title":"Clinical predictors of survival in metastatic uveal melanoma","volume":"63","author":"Lorenzo 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History"}},{"value":"2026-08-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70116"}}