{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:59:19Z","timestamp":1780412359250,"version":"3.54.1"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005366","name":"University of Oslo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005366","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The objective of this study was to analyze the diagnostic role of HEG homolog 1 (HEG1) in cancers affecting the serosal cavities. HEG1 protein expression by immunohistochemistry was analyzed in 534 specimens (341 effusions and 193 surgical specimens). Effusions consisted of 151 tubo-ovarian carcinomas, 59 breast carcinomas, 44 mesotheliomas, 37 lung carcinomas, 29 uterine corpus and cervical carcinomas, 17 gastrointestinal carcinomas and 4 genitourinary carcinomas. Surgical specimens consisted of 139 tubo-ovarian carcinomas, 42 mesotheliomas, 7 multicystic mesothelial proliferations and 5 papillary mesothelial tumors. HEG1 expression was found in 43\/44 (98%) mesothelioma effusions and 39\/42 (93%) surgical mesothelioma specimens, as well as all multicystic and papillary mesothelial tumors. HEG1 was infrequently expressed in breast carcinoma (4\/59; 7%), lung carcinoma (2\/37; 5%) and cervical\/uterine carcinoma effusions (3\/29; 10%), but was often detected in tubo-ovarian carcinoma effusions (80\/151; 53%) and surgical specimens (99\/139, 71%). HEG1 was additionally consistently expressed by reactive mesothelial cells in effusions and in endothelial cells in surgical specimens. HEG1 had sensitivity of 95% for diagnosing malignant mesothelioma in all studied specimens, with a specificity of 38% in the differential diagnosis from tubo-ovarian carcinoma and 93% in the differential diagnosis from non-tubo-ovarian carcinomas. Of 179 HEG1-positive carcinomas, 172 expressed the epithelial marker claudin-4. In conclusion, HEG1 is a highly sensitive marker of both benign and malignant mesothelial cells. It shows high specificity in the differentiation of mesothelioma from lung or breast carcinoma but is of little value in differentiating mesothelioma from tubo-ovarian carcinoma. The potential role of HEG1 as vascular marker merits further research.<\/jats:p>","DOI":"10.1007\/s00428-026-04438-w","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T02:33:18Z","timestamp":1770604398000},"page":"617-626","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The specificity of HEG1 as mesothelioma marker depends on the differential diagnosis"],"prefix":"10.1007","volume":"488","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-8427","authenticated-orcid":false,"given":"Ben","family":"Davidson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara Maria","family":"Stri\u010dak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arild","family":"Holth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Torgunrud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremias","family":"Wohlschlaeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"T\u00f6tsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assia","family":"Bassarova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"issue":"3","key":"4438_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74(3):229\u2013263. https:\/\/doi.org\/10.3322\/caac.21834","journal-title":"CA Cancer J Clin"},{"issue":"Suppl 1","key":"4438_CR2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41379-021-00895-7","volume":"35","author":"S Dacic","year":"2022","unstructured":"Dacic S (2022) Pleural mesothelioma classification-update and challenges. Mod Pathol 35(Suppl 1):51\u201356. https:\/\/doi.org\/10.1038\/s41379-021-00895-7","journal-title":"Mod Pathol"},{"key":"4438_CR3","doi-asserted-by":"publisher","DOI":"10.1038\/srep45768","volume":"7","author":"S Tsuji","year":"2017","unstructured":"Tsuji S, Washimi K, Kageyama T, Yamashita M, Yoshihara M, Matsuura R, Yokose T, Kameda Y, Hayashi H, Morohoshi T, Tsuura Y, Yusa T, Sato T, Togayachi A, Narimatsu H, Nagasaki T, Nakamoto K, Moriwaki Y, Misawa H, Hiroshima K, Miyagi Y, Imai K (2017) HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. Sci Rep 7:45768. https:\/\/doi.org\/10.1038\/srep45768","journal-title":"Sci Rep"},{"issue":"8","key":"4438_CR4","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1097\/PAS.0000000000001469","volume":"44","author":"JR Naso","year":"2020","unstructured":"Naso JR, Tsuji S, Churg A (2020) HEG1 is a highly specific and sensitive marker of epithelioid malignant mesothelioma. Am J Surg Pathol 44(8):1143\u20131148. https:\/\/doi.org\/10.1097\/PAS.0000000000001469","journal-title":"Am J Surg Pathol"},{"issue":"5","key":"4438_CR5","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/dc.24475","volume":"49","author":"K Hiroshima","year":"2021","unstructured":"Hiroshima K, Wu D, Hamakawa S, Tsuruoka S, Ozaki D, Orikasa H, Hasegawa M, Koh E, Sekine Y, Yonemori Y, Nabeshima K, Tsuji S, Miyagi Y, Imai K (2021) HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion. Diagn Cytopathol 49(5):622\u2013632. https:\/\/doi.org\/10.1002\/dc.24475","journal-title":"Diagn Cytopathol"},{"issue":"9","key":"4438_CR6","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1111\/pin.13140","volume":"71","author":"K Hiroshima","year":"2021","unstructured":"Hiroshima K, Wu D, Koh E, Sekine Y, Ozaki D, Yusa T, Nakazawa T, Tsuji S, Miyagi Y, Walts AE, Marchevsky AM, Husain AN, Imai K (2021) Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas. Pathol Int 71(9):604\u2013613. https:\/\/doi.org\/10.1111\/pin.13140","journal-title":"Pathol Int"},{"issue":"3","key":"4438_CR7","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1111\/his.14783","volume":"82","author":"A Churg","year":"2023","unstructured":"Churg A, Naso JR (2023) Hypothesis: HEG1 and claudin-4 staining will allow a diagnosis of epithelioid and biphasic mesothelioma versus non-small-cell lung carcinoma with only two stains in most cases. Histopathology 82(3):385\u2013392. https:\/\/doi.org\/10.1111\/his.14783","journal-title":"Histopathology"},{"key":"4438_CR8","doi-asserted-by":"crossref","unstructured":"Davidson B, Firat P, Michael CW (2018) Serous effusions - etiology, diagnosis, prognosis and therapy. 2nd ed. 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In Norway, study approval was given by the South-Eastern Norway Committee for Medical Research Ethics.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"None declared.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}