{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T15:01:05Z","timestamp":1778338865728,"version":"3.51.4"},"reference-count":38,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncology"],"published-print":{"date-parts":[[2019]]},"abstract":"<b><i>Objective:<\/i><\/b> Normally, activation of tropomyosin-related kinase (TRK) receptors by neurotrophins (NTs) stimulates intracellular pathways involved in cell survival and proliferation. Dysregulation of NT\/TRK signaling may affect neoplasm prognosis. Data on NT and TRK expression in melanomas are limited, and it is unclear whether NT\/TRK signaling pathways are involved in the origin and progression of this neoplasm. <b><i>Methods:<\/i><\/b> We examined whether NT\/TRK expression differs across different cutaneous melanoma grades and subtypes, and whether it is associated with melanoma prognosis and survival. A cross-sectional study was performed in which the expression of TrkA, TrkB, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) was analyzed by immunohistochemistry of 154 melanoma samples. We investigated NT\/TRK expression associations with prognostic factors for melanoma, relapse-free survival (RFS), and overall survival (OS). <b><i>Results:<\/i><\/b> Of the 154 melanoma samples, 77 (55.4%) were TrkA immunopositive, 81 (58.3%) were TrkB immunopositive, 113 (81.3%) were BDNF immunopositive, and 104 (75.4%) were NGF immunopositive. We found NT\/TRK expression associated strongly with several clinical prognostic factors, including the tumor-node-metastasis stage (<i>p<\/i> &#x3c; 0.001), histological subtype (<i>p<\/i> &#x3c; 0.001), and Clark level (<i>p<\/i> &#x3c; 0.05), as well as with a worse OS (<i>p<\/i> &#x3c; 0.05 for all, except TrkB) and RFS (<i>p<\/i> &#x3c; 0.05 for all). <b><i>Conclusions:<\/i><\/b> Our results show strong associations of NT\/TRK expression with melanoma stage progression and a poor prognosis.<\/jats:p>","DOI":"10.1159\/000499384","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T21:00:28Z","timestamp":1557435628000},"page":"26-37","source":"Crossref","is-referenced-by-count":15,"title":["Tropomyosin-Related Kinase Receptor and Neurotrophin Expression in Cutaneous Melanoma Is Associated with a Poor Prognosis and Decreased Survival"],"prefix":"10.1159","volume":"97","author":[{"given":"Lu\u00eds\u00a0Carlos\u00a0Moreira","family":"Antunes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Cartell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline\u00a0Brunetto","family":"de\u00a0Farias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato\u00a0Marchiori","family":"Bakos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Roesler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilberto","family":"Schwartsmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2019,5,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30122-X"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx176"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709684"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31601-X"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.06.028"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.43"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21935"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcsup.2013.07.012"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2014.02.007"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19981015)83:8<1664::AID-CNCR23>3.0.CO;2-G"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161629"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.8434.1"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(01)00530-4"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0560.2003.00068.x"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1791-y"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1309\/CHFHEYAT44WWP7J3"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.51.3002"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-1237"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/81.24.1893"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002\/path.861"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5433-z"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1038\/nature03890"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1038\/304596a0"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra062285"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2012.08.016"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30406-5"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-2494.2006.00321.x"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.21"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-009-9221-8"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1159\/000326564"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2867-11-23"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100944"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-015-0689-0"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1038\/jidsymp.1997.19"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1586\/era.11.150"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-160646"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8992"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714448"}],"container-title":["Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/499384","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/499384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:27:26Z","timestamp":1745425646000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000499384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,7,3]]},"published-print":{"date-parts":[[2019,7,9]]}},"URL":"https:\/\/doi.org\/10.1159\/000499384","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/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