{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T20:29:13Z","timestamp":1777062553776,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"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":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The spread and invasion of malignant melanoma cells involve degradation and reorganization of the extracellular matrix by the activation of several matrix metalloproteinases (MMPs). This study analyzed the expression of MMP\u20101, MMP\u20102, and MMP\u201013 proteins in primary nodular melanoma (NM) and dysplastic nevi (DN) as a significant risk factor for melanoma development. The secondary goal was to analyze the correlation of MMPs protein expression in NM with tumor invasion, <jats:italic>BRAF V600<\/jats:italic> mutation status, and overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemistry for MMP\u20101, MMP\u20102, and MMP\u201013 was performed on nodular melanoma (n = 52) and dysplastic nevi (n = 28) on tissue microarray (TMA). <jats:italic>BRAF V600<\/jats:italic> mutation analysis on NM samples was performed by the Sanger sequencing method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A high level of MMPs expression in NM samples (&gt;30%) compared with DN (&lt;8%) was statistically significant (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). <jats:italic>BRAF V600<\/jats:italic> mutations were detected in 15 of 39 (38.5%) NM samples. This study revealed an interesting finding that MMP\u20101 and MMP\u201013 protein expression in the <jats:italic>BRAF V600<\/jats:italic> mutated melanomas were significantly lower than in the <jats:italic>BRAF V600<\/jats:italic> wild type (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cox analysis revealed that Clark categories, Breslow thickness, and MMP\u20101 high protein expression are predictive factors for shorter overall survival (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec>","DOI":"10.1111\/cup.13603","type":"journal-article","created":{"date-parts":[[2019,11,2]],"date-time":"2019-11-02T08:54:07Z","timestamp":1572684847000},"page":"139-145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Matrix metalloproteinases MMP\u20101, MMP\u20102, and MMP\u201013 are overexpressed in primary nodular melanoma"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-1876","authenticated-orcid":false,"given":"Gordana","family":"Zamolo","sequence":"first","affiliation":[{"name":"Department of Pathology Faculty of Medicine, University of Rijeka  Rijeka Croatia"},{"name":"Department of Pathology Clinical Hospital Centre Rijeka  Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Grahovac","sequence":"additional","affiliation":[{"name":"Polyclinic of Dermatology, Gutenbergstr. 8, 87600  Kaufbeuren Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordana","family":"\u017dauhar","sequence":"additional","affiliation":[{"name":"Department of Physics University of Rijeka  Rijeka Croatia"},{"name":"Department of Medical Physics and Biophysics Faculty of Medicine, University of Rijeka  Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5804-0799","authenticated-orcid":false,"given":"Damir","family":"Vu\u010dini\u0107","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy and Oncology Clinical Hospital Centre Rijeka  Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Kova\u010d","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine, University of Rijeka  Rijeka Croatia"},{"name":"Department of Pathology Clinical Hospital Centre Rijeka  Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nika","family":"Brajeni\u0107","sequence":"additional","affiliation":[{"name":"The University of Rijeka Faculty of Medicine  Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bla\u017eenka","family":"Grahovac","sequence":"additional","affiliation":[{"name":"The University of Rijeka Faculty of Medicine  Rijeka Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1437206"},{"key":"e_1_2_7_3_1","first-page":"135","volume-title":"Pathology and Genetics of Skin Tumors","author":"LeBoit PE","year":"2006"},{"key":"e_1_2_7_4_1","volume-title":"Cancer Registry of the Croatian National Institute of Public Health","author":"\u0160ekerija M","year":"2015"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000123"},{"issue":"9","key":"e_1_2_7_6_1","first-page":"706","article-title":"Nodular melanoma. 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