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In primary and metastatic melanomas, VDR negatively correlated with nuclear HIF\u20101\u03b1 expression (<jats:italic>r\u00a0<\/jats:italic>=\u00a0\u2212.2273, <jats:italic>P\u00a0=\u00a0<\/jats:italic>.0302; <jats:italic>r\u00a0<\/jats:italic>=\u00a0\u2212.5081, <jats:italic>P\u00a0=\u00a0<\/jats:italic>.0011). Furthermore, the highest HIF\u20101\u03b1 expression was observed in pT3\u2010pT4 VDR\u2010negative melanomas. A comparative analysis of immunostained HIF\u20101\u03b1 and CYP27B1 and CYP24A1 showed lack of correlation between these parameters both in primary tumors and melanoma metastases. In contrast, ROR\u03b1 expression correlated positively with nuclear HIF\u20101\u03b1 expression in primary and metastatic lesions (<jats:italic>r\u00a0=\u00a0<\/jats:italic>.2438, <jats:italic>P\u00a0=\u00a0<\/jats:italic>.0175; <jats:italic>r\u00a0=\u00a0<\/jats:italic>.3662, <jats:italic>P\u00a0=\u00a0<\/jats:italic>.0166). Comparable levels of HIF\u20101\u03b1 expression pattern was observed in localized and advanced melanomas. ROR\u03b3 in primary melanomas correlated also positively with nuclear HIF\u20101\u03b1 expression (<jats:italic>r\u00a0=\u00a0<\/jats:italic>.2743, <jats:italic>P\u00a0=\u00a0<\/jats:italic>.0129). HIF\u20101\u03b1 expression was the lowest in localized ROR\u03b3\u2010negative melanomas. In addition, HIF\u20101\u03b1 expression correlated with ROR\u03b3\u2010positive lymphocytes in melanoma metastases. We further found that in metastatic lymph nodes FoxP3 immunostaining correlated positively with HIF\u20101\u03b1 and ROR\u03b3 expression in melanoma cells (<jats:italic>r\u00a0=\u00a0<\/jats:italic>.3667; <jats:italic>P\u00a0=\u00a0<\/jats:italic>.0327; <jats:italic>r\u00a0=\u00a0<\/jats:italic>.4208, <jats:italic>P\u00a0=\u00a0<\/jats:italic>.0129). In summary, our study indicates that the expression of VDR, ROR\u03b1 and ROR\u03b3 in melanomas is related to hypoxia and\/or HIF1\u2010\u03b1 activity, which also affects FoxP3 expression in metastatic melanoma. Therefore, the hypoxia can affect tumor biology by changing nuclear receptors expression and molecular pathways regulated by nuclear receptors and immune responses.<\/jats:p>","DOI":"10.1111\/exd.14002","type":"journal-article","created":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T15:25:06Z","timestamp":1562685906000},"page":"1036-1043","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["On the relationship between VDR, ROR\u03b1 and ROR\u03b3 receptors expression and HIF1\u2010\u03b1 levels in human melanomas"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-9965","authenticated-orcid":false,"given":"Anna A.","family":"Bro\u017cyna","sequence":"first","affiliation":[{"name":"Department of Human Biology, Faculty of Biology and Environmental Protection Nicolaus Copernicus University Toru\u0144 Poland"},{"name":"Department of Tumor Pathology and Pathomorphology Oncology Centre \u2013 Prof. Franciszek \u0141ukaszczyk Memorial Hospital Bydgoszcz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"J\u00f3\u017awicki","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology and Pathomorphology Oncology Centre \u2013 Prof. Franciszek \u0141ukaszczyk Memorial Hospital Bydgoszcz Poland"},{"name":"Department of Tumor Pathology and Pathomorphology, Faculty of Health Sciences Nicolaus Copernicus University Collegium Medicum in Bydgoszcz Bydgoszcz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton M.","family":"Jetten","sequence":"additional","affiliation":[{"name":"Cell Biology Section, Inflammation, Immunity and Disease Laboratory National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej T.","family":"Slominski","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Comprehensive Cancer Center Cancer Chemoprevention Program University of Alabama at Birmingham Birmingham AL USA"},{"name":"Laboratory Service of the VA Medical Center Birmingham AL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.3.1230"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.022"},{"key":"e_1_2_9_4_1","first-page":"4509","volume":"56","author":"Hockel M.","year":"1996","journal-title":"Can. 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