{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:02:51Z","timestamp":1765976571299,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"the Foundation for Science and Technology (FCT), Portugal","doi-asserted-by":"publisher","award":["PTDC\/MEC-ONC\/31384\/2017","UIDB\/00215\/2020","UIDP\/00215\/2020","LA\/P\/0064\/2020"],"award-info":[{"award-number":["PTDC\/MEC-ONC\/31384\/2017","UIDB\/00215\/2020","UIDP\/00215\/2020","LA\/P\/0064\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"the Foundation for Science and Technology (FCT), Portugal","doi-asserted-by":"publisher","award":["PTDC\/MEC-ONC\/31384\/2017","UIDB\/00215\/2020","UIDP\/00215\/2020","LA\/P\/0064\/2020"],"award-info":[{"award-number":["PTDC\/MEC-ONC\/31384\/2017","UIDB\/00215\/2020","UIDP\/00215\/2020","LA\/P\/0064\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"the Foundation for Science and Technology (FCT), Portugal","doi-asserted-by":"publisher","award":["PTDC\/MEC-ONC\/31384\/2017","UIDB\/00215\/2020","UIDP\/00215\/2020","LA\/P\/0064\/2020"],"award-info":[{"award-number":["PTDC\/MEC-ONC\/31384\/2017","UIDB\/00215\/2020","UIDP\/00215\/2020","LA\/P\/0064\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"the Foundation for Science and Technology (FCT), Portugal","doi-asserted-by":"publisher","award":["PTDC\/MEC-ONC\/31384\/2017","UIDB\/00215\/2020","UIDP\/00215\/2020","LA\/P\/0064\/2020"],"award-info":[{"award-number":["PTDC\/MEC-ONC\/31384\/2017","UIDB\/00215\/2020","UIDP\/00215\/2020","LA\/P\/0064\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The differential diagnosis between adrenocortical adenomas (ACAs) and adrenocortical carcinomas (ACCs) relies on unspecific clinical, imaging and histological features, and, so far, no single molecular biomarker has proved to improve diagnostic accuracy. Similarly, prognostic factors have an insufficient capacity to predict the heterogeneity of ACC clinical outcomes, which consequently lead to inadequate treatment strategies. Angiogenesis is a biological process regulated by multiple signaling pathways, including VEGF and the Ang\u2013Tie pathway. Many studies have stressed the importance of angiogenesis in cancer development and metastasis. In the present study, we evaluated the expression of VEGF and Ang\u2013Tie pathway mediators in adrenocortical tumors (ACTs), with the ultimate goal of assessing whether these molecules could be useful biomarkers to improve diagnostic accuracy and\/or prognosis prediction in ACC. The expression of the proteins involved in angiogenesis, namely CD34, VEGF, VEGF-R2, Ang1, Ang2, Tie1 and Tie2, was assessed by immunohistochemistry in ACC (n = 22), ACA with Cushing syndrome (n = 8) and non-functioning ACA (n = 13). ACC presented a significantly higher Ang1 and Ang2 expression when compared to ACA. Tie1 expression was higher in ACC with venous invasion and in patients with shorter overall survival. In conclusion, although none of these biomarkers showed to be useful for ACT diagnosis, the Ang\u2013Tie pathway is active in ACT and may play a role in regulating ACT angiogenesis.<\/jats:p>","DOI":"10.3390\/ijms23105579","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T04:04:19Z","timestamp":1652760259000},"page":"5579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ang\u2013Tie Angiogenic Pathway Is Distinctively Expressed in Benign and Malignant Adrenocortical Tumors"],"prefix":"10.3390","volume":"23","author":[{"given":"Sofia","family":"Oliveira","sequence":"first","affiliation":[{"name":"UMIB\u2013Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2013Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4560","authenticated-orcid":false,"given":"Sofia S.","family":"Pereira","sequence":"additional","affiliation":[{"name":"UMIB\u2013Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2013Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, 4050-313 Porto, Portugal"},{"name":"ITR\u2013Laboratory for Integrative and Translational Research in Population Health, 4050-600 Porto, Portugal"}]},{"given":"Madalena M.","family":"Costa","sequence":"additional","affiliation":[{"name":"UMIB\u2013Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2013Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, 4050-313 Porto, Portugal"},{"name":"ITR\u2013Laboratory for Integrative and Translational Research in Population Health, 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-1831","authenticated-orcid":false,"given":"Mariana P.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"UMIB\u2013Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2013Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, 4050-313 Porto, Portugal"},{"name":"ITR\u2013Laboratory for Integrative and Translational Research in Population Health, 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5555-7004","authenticated-orcid":false,"given":"Duarte","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, 4200-135 Porto, Portugal"},{"name":"Department of Endocrinology, Hospital S. Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.cancergen.2012.02.009","article-title":"The molecular basis of adrenocortical cancer","volume":"205","author":"Lehmann","year":"2012","journal-title":"Cancer Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pignatelli, D. (2011). Adrenal Cortex Tumors and Hyperplasias. Contemporary Aspects of Endocrinology, IntechOpen.","DOI":"10.5772\/19108"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.humpath.2009.03.010","article-title":"The Weiss system for evaluating adrenocortical neoplasms: 25 years later","volume":"40","author":"Lau","year":"2009","journal-title":"Hum. 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