{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:06:15Z","timestamp":1787785575894,"version":"build-2784847793"},"reference-count":24,"publisher":"Mattioli1885","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dermatol Pract Concept"],"abstract":"<jats:p>Background:\u00a0BRAF\u00a0mutations are a common finding in malignant melanoma (MM). Nevertheless, apart from their significance as a therapeutic target in advanced melanoma, their prognostic value is still debated.Objective:\u00a0To assess BRAF\u00a0mutation status in primary, recurrent, or metastatic MM and its correlations with histopathological findings.Methods:\u00a0We analyzed 203 samples from 178 consecutive patients: 129 primary cutaneous MM, 49 metastatic and recurrent MM of unknown primary site, and 25 cases of recurrences or metastases of primary MM. BRAF\u00a0mutations in exon 15 were identified with real-time polymerase chain reaction and\/or direct sequencing or pyrosequencing. Histopathological examination was performed according to standard procedures.Results:\u00a0We observed a 42.1% prevalence of BRAF\u00a0mutations at codon 600 among our patients, 84% of whom harbored the V600E mutation. Mutations showed a statistically significant increase in younger patients (P = 0.011), in ulcerated tumors (P = 0.020), and in tumors lacking solar elastosis in adjacent dermis (P = 0.008). Mutations were also more common in male patients, as well as in primary MMs of the torso, and in nonvisceral metastases, however without reaching statistical significance. Logistic regression analysis identified type and ulceration as the only significant predictors of BRAF\u00a0mutation. The highest frequencies of mutated BRAF\u00a0were identified in superficial spreading and nodular types, and the lowest in acral lentiginous and lentigo maligna types. In situ MM and primary dermal melanoma displayed intermediate frequencies.Conclusion:\u00a0Frequency of mutated BRAF\u00a0is type-related and correlated with ulceration, a known adverse prognostic factor.<\/jats:p>","DOI":"10.5826\/dpc.0901a13","type":"journal-article","created":{"date-parts":[[2019,3,10]],"date-time":"2019-03-10T21:53:06Z","timestamp":1552254786000},"page":"54-62","source":"Crossref","is-referenced-by-count":30,"title":["BRAF Mutation Status in Primary, Recurrent, and Metastatic Malignant Melanoma and Its Relation to Histopathological Parameters"],"prefix":"10.5826","author":[{"given":"Aris","family":"Spathis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander C","family":"Katoulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-8833","authenticated-orcid":false,"given":"Vasileia","family":"Damaskou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3936-8374","authenticated-orcid":false,"given":"Aikaterini I.","family":"Liakou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0979-3871","authenticated-orcid":false,"given":"Christine","family":"Kottaridi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-7843","authenticated-orcid":false,"given":"Danai","family":"Leventakou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0009-8821","authenticated-orcid":false,"given":"Dimitrios","family":"Sgouros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Mamantopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Rigopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2957-6850","authenticated-orcid":false,"given":"Petros","family":"Karakitsos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6394-117X","authenticated-orcid":false,"given":"Ioannis G.","family":"Panayiotides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27750","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30.","DOI":"10.3322\/caac.21387"},{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-954.","DOI":"10.1038\/nature00766"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Busc\u00e0 R, Abbe P, Mantoux F, et al. Ras mediates the cAMP-dependent activation of extracellular signal-regulated kinases (ERKs) in melanocytes. EMBO J. 2000;19(12):2900-2910.","DOI":"10.1093\/emboj\/19.12.2900"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Poynter JN, Elder JT, Fullen DR, et al. BRAF and NRAS mutations in melanoma and melanocytic nevi. Melanoma Res. 2006;16(4):267-273.","DOI":"10.1097\/01.cmr.0000222600.73179.f3"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Arozarena I, Sanchez-Laorden B, Packer L, et al. Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A. Cancer Cell. 2011;19(1):45-57.","DOI":"10.1016\/j.ccr.2010.10.029"},{"key":"ref5","unstructured":"Dong J, Phelps RG, Qiao R, et al. BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma. Cancer Res. 2003;63(14): 3883-3885."},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Shinozaki M, Fujimoto A, Morton DL, Hoon DSB. Incidence of BRAF oncogene mutation and clinical relevance for primary cutaneous melanomas. Clin Cancer Res. 2004;10(5):1753-1757.","DOI":"10.1158\/1078-0432.ccr-1169-3"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Barbour AP, Tang YH, Armour N, et al. BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma: implications for melanoma staging and adjuvant therapy. Eur J Cancer. 2014;50(15):2668-2676.","DOI":"10.1016\/j.ejca.2014.06.009"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363(9):809\u2013819.","DOI":"10.1056\/nejmoa1002011"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Balch CM, Soong S-J, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on cancer melanoma staging system. J Clin Oncol. 2001;19(16):3622-3634.","DOI":"10.1200\/JCO.2001.19.16.3622"},{"key":"ref10","unstructured":"Spathis A, Georgoulakis J, Foukas P, et al. KRAS and BRAF mutation analysis from liquid-based cytology brushings of colorectal carcinoma in comparison with formalin-fixed, paraffin-embedded tissue. Anticancer Res. 2010;30(6):1969-1975."},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Ellerhorst JA, Greene VR, Ekmekcioglu S, et al. Clinical correlates of NRAS and BRAF mutations in primary human melanoma. Clin Cancer Res. 2011;17(2):229\u2013235.","DOI":"10.1158\/1078-0432.ccr-10-2276"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Jakob JA, Bassett RL Jr, Ng CS, et al. NRAS mutation status is an independent prognostic factor in metastatic melanoma. Cancer. 2012;118(16):4014-4023.","DOI":"10.1002\/cncr.26724"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Colombino M, Capone M, Lissia A, et al. BRAF\/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma. J Clin Oncol. 2012;30(20):2522-2529.","DOI":"10.1200\/JCO.2011.41.2452"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Lee JH, Choi JW, Kim YS. Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis. Br J Dermatol. 2011;164(4):776-784.","DOI":"10.1111\/j.1365-2133.2010.10185.x"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Kim SY, Kim SN, Hahn HJ, Lee YW, Choe YB, Ahn KJ. Metaanalysis of BRAF mutations and clinicopathologic characteristics in primary melanoma. J Am Acad Dermatol. 2015;72(6):1036-1046.e2.","DOI":"10.1016\/j.jaad.2015.02.1113"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Yamazaki N, Tanaka R, Tsutsumida A, et al. BRAF V600 mutations and pathological features in Japanese melanoma patients. Melanoma Res. 2015;25(1):9-14.","DOI":"10.1097\/cmr.0000000000000091"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Mooi WJ, Krausz T. Melanoma: subtypes and variants. In: Hodder A, ed. Pathology of Melanocytic Disorders. London: Taylor & Francis Ltd. 2007:285-342.","DOI":"10.1201\/b13561-14"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Safaee Ardekani G, Jafarnejad SM, Khosravi S, Martinka M, Ho V, Li G. Disease progression and patient survival are significantly influenced by BRAF protein expression in primary melanoma. Br J Dermatol. 2013;169(2):320-328.","DOI":"10.1111\/bjd.12351"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Akslen LA, Angelini S, Straume O, et al. BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival. J Invest Dermatol. 2005;125(2):312-317.","DOI":"10.1111\/j.0022-202x.2005.23788.x"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Hugdahl E, Kalvenes MB, Puntervoll HE, Ladstein RG, Akslen LA. BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival. Br J Cancer. 2016;114(7):801-808.","DOI":"10.1038\/bjc.2016.44"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Shen S, Wolfe R, McLean CA, Haskett M, Kelly JW. Characteristics and associations of high-mitotic-rate melanoma. JAMA Dermatol. 2014;150(10):1048-1055.","DOI":"10.1001\/jamadermatol.2014.635"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Greene VR, Johnson MM, Grimm EA, Ellerhorst JA. Frequencies of NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma. J Invest Dermatol. 2009;129(6):1483\u20131488. Mar VJ, Liu W, Devitt B, et al. The role of BRAF mutations in primary melanoma growth rate and survival. Br J Dermatol. 2015;173(1):76-82.","DOI":"10.1038\/jid.2008.374"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Akbani R, Akdemir KC, Aksoy AA, et al; Cancer Genome Atlas Network. Genomic Classification of Cutaneous Melanoma. Cell. 2015;161(7):1681-1696.","DOI":"10.1016\/j.cell.2015.05.044"}],"container-title":["Dermatology Practical &amp; Conceptual"],"original-title":[],"link":[{"URL":"https:\/\/dpcj.org\/index.php\/dpc\/article\/download\/dermatol-pract-concept-articleid-dp0901a13\/dp0901a13-pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dpcj.org\/index.php\/dpc\/article\/download\/dermatol-pract-concept-articleid-dp0901a13\/352","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dpcj.org\/index.php\/dpc\/article\/download\/dermatol-pract-concept-articleid-dp0901a13\/dp0901a13-pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T13:14:36Z","timestamp":1708434876000},"score":1,"resource":{"primary":{"URL":"https:\/\/dpcj.org\/index.php\/dpc\/article\/view\/dermatol-pract-concept-articleid-dp0901a13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,31]]},"references-count":24,"URL":"https:\/\/doi.org\/10.5826\/dpc.0901a13","relation":{},"ISSN":["2160-9381"],"issn-type":[{"value":"2160-9381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,31]]}}}