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This limitation is particularly evident among pulmonary carcinoids, a subgroup characterized by highly variable clinical behaviour and prognostic outcomes despite similar morphological features.<\/jats:p>\n                  <jats:p>Angiogenesis is a hallmark of NENs, yet the role of the vascular endothelial growth factor (VEGF) pathway in pulmonary NENs remains incompletely defined.<\/jats:p>\n                  <jats:p>In this multicentre retrospective study, 109 pulmonary NENs (67 typical carcinoids, 22 atypical carcinoids, and 20 high-grade NENs) were analysed. VEGF, VEGFR1, VEGFR2, and VEGFR3 expression was assessed by immunohistochemistry and correlated with clinicopathological features and outcome.<\/jats:p>\n                  <jats:p>VEGF pathway components showed subtype-specific expression patterns. VEGFR1 was reduced in high-grade tumours and displayed a bimodal distribution, while VEGFR2 and VEGFR3 were higher in atypical carcinoids and high-grade tumours. Survival and recurrence were driven by histological subtype, whereas VEGF pathway expression lacked independent prognostic significance.<\/jats:p>\n                  <jats:p>The higher expression of VEGFR2 and VEGFR3 observed in atypical carcinoids and high-grade neuroendocrine carcinomas suggests a possible involvement of the VEGF signalling pathway in tumour biology. These findings contribute to the biological characterization of pulmonary NENs and provide a rationale for future studies investigating whether VEGF pathway markers may have predictive relevance for anti-angiogenic therapies.<\/jats:p>","DOI":"10.1007\/s00428-026-04713-w","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:38:28Z","timestamp":1791257908000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["VEGF pathway signalling across pulmonary neuroendocrine tumours: associations with histological subtypes in a multicentre study"],"prefix":"10.1007","author":[{"given":"F.","family":"Pezzuto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Fortarezza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Vedovelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Comacchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Quaranta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Andaloro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"De Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Marzullo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Pasello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Gregori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Dell\u2019Amore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Pelosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Serio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-9226","authenticated-orcid":false,"given":"F.","family":"Calabrese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"4713_CR1","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1001\/jamaoncol.2017.0589","volume":"3","author":"A Dasari","year":"2017","unstructured":"Dasari A, Shen C, Halperin D et al (2017) Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. 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