{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T15:23:16Z","timestamp":1785684196774,"version":"3.56.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T00:00:00Z","timestamp":1517875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Harboe Foundation"},{"name":"Henny Sophie Clausen og m\u00f8belarkitekt Clausens Fond"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The aims of the present study were to analyse the usability of an immunohistochemical (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>) analysis as compared with a frequently used mutation detection analysis, and to examine the extent of intratumour and intertumour heterogeneity of <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> V600E in primary tumours and their corresponding metastases. In the development of intertumour heterogeneity between the primary tumour and the corresponding metastases, time as a factor was also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>In total, 227 samples from 224 melanoma patients were analysed with both the Cobas 4800 <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> V600 Mutation Test and <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> anti\u2010<jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> V600E staining. In 82 primary tumours and 224 corresponding metastases, the extents of intertumour and intratumour heterogeneity were investigated with <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> staining. In 15 cases, disagreement between <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> analysis and the Cobas test was seen. In all but one of the examined patients, homogeneity between the primary tumour and the corresponding metastasis was found. Except for this one case, no heterogeneity developed over longer periods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> analysis can be safely used as a <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> pretreatment screening tool, and no additional test is needed when staining is positive. However, if stains are negative, additional tests are essential for detection of other <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> mutations. We suggest that using primary melanoma tissues is just as safe as using metastatic tissue for detection of <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> V600E, as <jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content> intertumour heterogeneity is extremely rare. In addition, the time between diagnosis of the primary tumour and diagnosis of the corresponding metastasis seems not to increase the risk of intertumour heterogeneity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13431","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T01:22:42Z","timestamp":1510190562000},"page":"814-825","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Concordance in <scp>BRAF<\/scp> V600E status over time in malignant melanoma and corresponding metastases"],"prefix":"10.1111","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6157-2112","authenticated-orcid":false,"given":"Line B","family":"Nielsen","sequence":"first","affiliation":[{"name":"Department of Pathology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Dabrosin","sequence":"additional","affiliation":[{"name":"Department of Pathology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Sloth","sequence":"additional","affiliation":[{"name":"Department of Pathology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L","family":"B\u00f8nnelykke\u2013Behrndtz","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Steiniche","sequence":"additional","affiliation":[{"name":"Department of Pathology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne","family":"Lade\u2010Keller","sequence":"additional","affiliation":[{"name":"Department of Pathology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,6]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"LucasR McMichaelT SmithW ArmstrongB.World Health Organization.Solar ultraviolet radiation: global burden of disease from solar ultraviolet radiation. 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