{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:53:42Z","timestamp":1790045622590,"version":"4.0.1"},"reference-count":0,"publisher":"Bioscientifica","issue":"10","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:p>\n                    Adrenocortical carcinoma (ACC) is diagnosed using the histopathological Weiss score (WS), but remains clinically elusive unless it has metastasized or grows locally invasive. Previously, we proposed the objective IGF2 methylation score as diagnostic tool for ACC. This multicenter European cohort study validates these findings. Patient and tumor characteristics were obtained from adrenocortical tumor patients. DNA was isolated from frozen specimens, where after DMR2, CTCF3, and H19 were pyrosequenced. The predictive value of the methylation score for malignancy, defined by the WS or metastasis development, was assessed using receiver operating characteristic curves and logistic and Cox regression analyses. Seventy-six ACC patients and 118 patients with adrenocortical adenomas were included from seven centers. The methylation score and tumor size were independently associated with the pathological ACC diagnosis (OR 3.756 95% CI 2.224\u20136.343; OR 1.467 95% CI 1.202\u20131.792, respectively; Hosmer\u2013Lemeshow test\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.903), with an area under the curve (AUC) of 0.957 (95% CI 0.930\u20130.984). The methylation score alone resulted in an AUC of 0.910 (95% CI 0.866\u20130.952). Cox regression analysis revealed that the methylation score, WS and tumor size predicted development of metastases in univariate analysis. In multivariate analysis, only the WS predicted development of metastasis (OR 1.682 95% CI 1.285\u20132.202;\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001). In conclusion, we validated the high diagnostic accuracy of the IGF2 methylation score for diagnosing ACC in a multicenter European cohort study. Considering the known limitations of the WS, the objective IGF2 methylation score could potentially provide extra guidance on decisions on postoperative strategies in adrenocortical tumor patients.\n                  <\/jats:p>","DOI":"10.1530\/erc-19-0378","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T14:01:24Z","timestamp":1594821684000},"page":"541-550","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":6,"title":["The IGF2 methylation score for adrenocortical cancer: an ENSAT validation study"],"prefix":"10.1530","volume":"27","author":[{"given":"S G","family":"Creemers","sequence":"first","affiliation":[{"name":"1Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"Feelders","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Valdes","sequence":"additional","affiliation":[{"name":"2Servicio de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario de Asturias, Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C L","family":"Ronchi","sequence":"additional","affiliation":[{"name":"3Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"4Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Volante","sequence":"additional","affiliation":[{"name":"5Department of Oncology, University of Turin, Orbassano, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B M","family":"van Hemel","sequence":"additional","affiliation":[{"name":"6Department of Pathology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Luconi","sequence":"additional","affiliation":[{"name":"7Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences \u2018Mario Serio\u2019, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M H T","family":"Ettaieb","sequence":"additional","affiliation":[{"name":"8Departments of Internal Medicine and Endocrinology, M\u00e1xima Medical Center, Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Mannelli","sequence":"additional","affiliation":[{"name":"7Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences \u2018Mario Serio\u2019, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M D","family":"Chiara","sequence":"additional","affiliation":[{"name":"9Instituto Universitario de Oncologia del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Fassnacht","sequence":"additional","affiliation":[{"name":"10Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Papotti","sequence":"additional","affiliation":[{"name":"5Department of Oncology, University of Turin, Orbassano, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M N","family":"Kerstens","sequence":"additional","affiliation":[{"name":"11Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Nesi","sequence":"additional","affiliation":[{"name":"12Division of Pathological Anatomy, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H R","family":"Haak","sequence":"additional","affiliation":[{"name":"8Departments of Internal Medicine and Endocrinology, M\u00e1xima Medical Center, Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F J","family":"van Kemenade","sequence":"additional","affiliation":[{"name":"13Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L J","family":"Hofland","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/27\/10\/ERC-19-0378.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/27\/10\/ERC-19-0378.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:28Z","timestamp":1784555728000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/27\/10\/541-550\/25344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":0,"journal-issue":{"issue":"10"},"URL":"https:\/\/doi.org\/10.1530\/erc-19-0378","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}