{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:53:33Z","timestamp":1778756013627,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T00:00:00Z","timestamp":1465948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Background and aims<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content><\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content><\/jats:italic> mutations occur in approximately 60% of cutaneous melanomas, and the identification of such mutations underpins the appropriate selection of patients who may benefit from <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">MEK<\/jats:styled-content> inhibitor targeted therapies. The utility of immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>) to detect <jats:italic>NRAS<\/jats:italic><jats:sup>Q61L<\/jats:sup> mutations is currently unknown. This study sought to assess the sensitivity and specificity of anti\u2010BRAF<jats:sup>V600E<\/jats:sup> (<jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>1), anti\u2010NRAS<jats:sup>Q61R<\/jats:sup> (<jats:styled-content style=\"fixed-case\">SP<\/jats:styled-content>174) and anti\u2010NRAS<jats:sup>Q61L<\/jats:sup> (26193) antibodies for mutation detection in a large series of cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Mutation status was determined using the OncoCarta assay in 754 cutaneous melanomas. <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> with the anti\u2010BRAF<jats:sup>V600E<\/jats:sup> antibody was performed in all cases, and the anti\u2010NRAS<jats:sup>Q61R<\/jats:sup> and anti\u2010NRAS<jats:sup>Q61L<\/jats:sup> antibodies were assessed in a subset of 302 samples utilizing tissue microarrays. The staining with the anti\u2010BRAF<jats:sup>V600E<\/jats:sup> and anti\u2010NRAS<jats:sup>Q61R<\/jats:sup> antibodies was diffuse, homogeneous and cytoplasmic. The anti\u2010NRAS<jats:sup>Q61L<\/jats:sup> antibody displayed variable intensity staining, ranging from weak to strong in <jats:italic>NRAS<\/jats:italic><jats:sup>Q61L<\/jats:sup> mutant tumours. The sensitivity and specificity for anti\u2010BRAF<jats:sup>V600E<\/jats:sup> was 100 and 99.3%, anti\u2010NRAS<jats:sup>Q61R<\/jats:sup> was 100 and 100% and anti\u2010NRAS<jats:sup>Q61L<\/jats:sup> was 82.6 and 96.2%, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The use of <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> is a fast, efficient and cost\u2010effective method to identify single specific mutations in melanoma patients. BRAF<jats:sup>V600E<\/jats:sup> and NRAS<jats:sup>Q61R<\/jats:sup> antibodies have high sensitivity and specificity; however, the NRAS<jats:sup>Q61L<\/jats:sup> antibody appears less sensitive. <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> can help to facilitate the timely, appropriate selection and treatment of metastatic melanoma patients with targeted therapies. Detection of melanoma\u2010associated mutations by <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> may also provide evidence for a diagnosis of melanoma in metastatic undifferentiated neoplasms lacking expression of melanoma antigens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12992","type":"journal-article","created":{"date-parts":[[2016,5,6]],"date-time":"2016-05-06T07:58:48Z","timestamp":1462521528000},"page":"680-686","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["<i>BRAF<\/i><sup>V600E<\/sup> and <i>NRAS<\/i><sup>Q61L\/Q61R<\/sup> mutation analysis in metastatic melanoma using immunohistochemistry: a study of 754 cases highlighting potential pitfalls and guidelines for interpretation and reporting"],"prefix":"10.1111","volume":"69","author":[{"given":"Hojabr","family":"Kakavand","sequence":"first","affiliation":[{"name":"Melanoma Institute Australia North Sydney NSW Australia"},{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Walker","sequence":"additional","affiliation":[{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"},{"name":"Tissue Pathology and Diagnostic Oncology Royal Prince Alfred Hospital Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trina","family":"Lum","sequence":"additional","affiliation":[{"name":"Tissue Pathology and Diagnostic Oncology Royal Prince Alfred Hospital Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James S","family":"Wilmott","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia North Sydney NSW Australia"},{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina I","family":"Selinger","sequence":"additional","affiliation":[{"name":"Tissue Pathology and Diagnostic Oncology Royal Prince Alfred Hospital Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Smith","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia North Sydney NSW Australia"},{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn P M","family":"Saw","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia North Sydney NSW Australia"},{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Yu","sequence":"additional","affiliation":[{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"},{"name":"Medical Genomics Royal Prince Alfred Hospital Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy A","family":"Cooper","sequence":"additional","affiliation":[{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"},{"name":"Tissue Pathology and Diagnostic Oncology Royal Prince Alfred Hospital Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgina V","family":"Long","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia North Sydney NSW Australia"},{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"},{"name":"Melanoma Oncology Royal North Shore and Mater Hospital Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra A","family":"O'Toole","sequence":"additional","affiliation":[{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"},{"name":"Tissue Pathology and Diagnostic Oncology Royal Prince Alfred Hospital Camperdown NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A","family":"Scolyer","sequence":"additional","affiliation":[{"name":"Melanoma Institute Australia North Sydney NSW Australia"},{"name":"Sydney Medical School The University of Sydney Camperdown NSW Australia"},{"name":"Tissue Pathology and Diagnostic Oncology Royal Prince Alfred Hospital Camperdown NSW 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