{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:51:17Z","timestamp":1789847477924,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,9,14]],"date-time":"2013-09-14T00:00:00Z","timestamp":1379116800000},"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":["Histopathology"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Tumour\u2010infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>s) are specialized vessels present in lymph nodes and tertiary lymphoid organs. <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>19, <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>21 and <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>7 regulate lymphocyte migration through <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>s. The aim of our study was to correlate <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with <jats:italic><jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>19<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>21<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>7<\/jats:italic> m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>High endothelial venule density was evaluated by immunohistochemistry with a specific antibody, <jats:styled-content style=\"fixed-case\">MECA<\/jats:styled-content>\u201079, and chemokine expression was evaluated by real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">MECA<\/jats:styled-content>\u201079\u2010positive vessels, covered by cuboidal (<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>) or flat (<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>) endothelium, were detected in 55% of melanomas. <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> density was higher in primary melanomas than in metastases. Positive correlations were found between <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> density and lymphocytic infiltration, and between <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> density and tumour regression. Cases in which the number of <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>s exceeded that of <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>s had higher levels of <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>19, <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>21, and <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results support a predominant role for <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> in the recruitment of lymphocytes in cutaneous melanomas, mediated by <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>19 and <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>21, whereas the density of <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content> strongly correlates with tumour regression, Therefore, cuboidal and flat <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>s may serve as indicators of the active and late quiescent phases, respectively, of tumour regression in cutaneous malignant melanoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12235","type":"journal-article","created":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T18:00:26Z","timestamp":1374688826000},"page":"852-861","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["The density and type of <scp>MECA<\/scp>\u201079\u2010positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous melanoma"],"prefix":"10.1111","volume":"63","author":[{"given":"Gabriela","family":"Avram","sequence":"first","affiliation":[{"name":"Department of Pathology University of Valencia Valencia Spain"},{"name":"Department of Cellular and Molecular Biology University of Medicine and Pharmacy Craiova Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"S\u00e1nchez\u2010Sendra","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Department Hospital Cl\u00ednico Universitario INCLIVA Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Dermatology Department Hospital Cl\u00ednico Universitario INCLIVA Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liria","family":"Terr\u00e1dez","sequence":"additional","affiliation":[{"name":"Manises Hospital Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Valencia Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Monteagudo","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Valencia Valencia Spain"},{"name":"Anatomic Pathology Department Hospital Cl\u00ednico Universitario INCLIVA Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2004.05708.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp252"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077241"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.21.1588"},{"key":"e_1_2_6_6_1","first-page":"449","article-title":"High endothelial venules","volume":"16","author":"Gauguet JM","year":"1995","journal-title":"Immunol. 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