{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:34:54Z","timestamp":1791135294717,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Tyrosine kinase inhibitors (TKIs) are evaluated for treatment of radioiodine refractory thyroid cancer. Their effects in this setting are based on blockade of proangiogenic signaling mediated by receptors for vascular endothelial growth factors (VEGFs) and platelet-derived growth factors (PDGF). Most TKIs also block other cancer-relevant kinases, such as B-type Raf kinase (BRAF), which are constitutively activated in approximately half of papillary thyroid carcinomas (PTCs), but the impact of these effects is not clear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>The aim of our study was to investigate the impact of <jats:italic>BRAF<\/jats:italic><jats:sup><jats:italic>V600E<\/jats:italic><\/jats:sup> on proangiogenic gene expression and microvascular features of PTCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>mRNA levels for <jats:italic>VEGFA, VEGF<\/jats:italic> receptors, and coreceptors (<jats:italic>VEGFRs<\/jats:italic> 1, 2, and 3, neuropilin-1), and PDGF receptor \u03b2 (<jats:italic>PDGFR<\/jats:italic><jats:italic>\u03b2<\/jats:italic> or <jats:italic>PDGFRB<\/jats:italic>) were measured with real-time PCR in <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> (<jats:italic>n<\/jats:italic>=55) and wild-type <jats:italic>BRAF<\/jats:italic> (<jats:italic>BRAF<\/jats:italic>-wt; <jats:italic>n<\/jats:italic>=35) PTCs. VEGF and VEGFR protein expression and microvessel densities (MVD) and lymphatic vessel densities (LVDs) were assessed by immunohistochemistry in 22 of the 90 PTCs (including 11 <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> cases). Angiogenic gene expression was also studied <jats:italic>in vitro<\/jats:italic> after induction\/silencing of the <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> mutation in thyrocyte lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transcript levels of proangiogenic factors were significantly lower in <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> PTCs versus <jats:italic>BRAF<\/jats:italic>-wt PTCs (<jats:italic>P<\/jats:italic>&lt;0.0001), but MVD and LVDs were not significantly different. <jats:italic>VEGFA<\/jats:italic> mRNA levels in thyroid cell lines decreased when <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> mutation was induced (<jats:italic>P<\/jats:italic>=0.01) and increased when it was silenced (<jats:italic>P<\/jats:italic>=0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Compared with <jats:italic>BRAF<\/jats:italic>-wt PTCs, those harboring <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> exhibit downregulated <jats:italic>VEGFA, VEGFR<\/jats:italic>, and <jats:italic>PDGFR<\/jats:italic><jats:italic>\u03b2<\/jats:italic> expression, suggesting that the presence of BRAF mutation does not imply a stronger prediction of response to drugs targeting VEGF and PDGFB signaling pathways.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-11-0283","type":"journal-article","created":{"date-parts":[[2011,6,9]],"date-time":"2011-06-09T04:35:33Z","timestamp":1307594133000},"page":"455-463","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":26,"title":["BRAFV600E mutation and expression of proangiogenic molecular markers in papillary thyroid carcinomas"],"prefix":"10.1093","volume":"165","author":[{"given":"Cosimo","family":"Durante","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Tallini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efisio","family":"Puxeddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialuisa","family":"Sponziello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ligorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cavaliere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry J","family":"Rhoden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Verrienti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Maranghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Giacomelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Filetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"11","key":"1_35881622","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1089\/thy.2009.0110","volume":"19","author":"Cooper","year":"2009","journal-title":"Thyroid : official journal of the American Thyroid Association","ISSN":"https:\/\/id.crossref.org\/issn\/1050-7256","issn-type":"print"},{"issue":"5","key":"2_10551783","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1530\/eje.0.1430623","volume":"143","author":"Arturi","year":"2000","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"8","key":"3_22077700","doi-asserted-by":"publisher","first-page":"2892","DOI":"10.1210\/jc.2005-2838","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; 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