{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T13:12:27Z","timestamp":1772284347036,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T00:00:00Z","timestamp":1414627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Hepatocellular adenomas (<jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content>) are rare, benign liver tumours that often occur in women of reproductive age. <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content> has been associated with the use of oral contraceptives, but the increased incidence of the tumour in older women and in men has linked the tumour type to other diseases, including the metabolic syndrome. Genotypical classification of the adenomas has led to the identification of four subgroups that correlate genotype with phenotype: human hepatocyte nuclear factor\u20101 alpha (<jats:styled-content style=\"fixed-case\">HNF<\/jats:styled-content>1\u03b1) inactivating <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content>, \u03b2\u2010catenin activating <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content>, inflammatory <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content> and unclassified <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">HNF<\/jats:styled-content>1\u03b1 inactivating <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content> is associated with bi\u2010allelic mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">TCF<\/jats:styled-content>1<\/jats:italic> gene and morphologically has marked steatosis. \u03b2\u2010catenin activating <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content> has increased activity of the <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>nt\/\u03b2\u2010catenin pathway and is associated with possible malignant transformation. Inflammatory <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content> is characterized by an oncogene\u2010induced inflammation due to alterations in the Janus kinase\/signal transducer and activator of transcription (<jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>) pathway. In the diagnostic setting, sub classification of <jats:styled-content style=\"fixed-case\">HCA<\/jats:styled-content> is based primarily on immunohistochemical analyzes, and has had an increasing impact on choice of treatment and individual prognostic assessment. This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value.<\/jats:p>","DOI":"10.1111\/his.12539","type":"journal-article","created":{"date-parts":[[2014,9,6]],"date-time":"2014-09-06T07:21:30Z","timestamp":1409988090000},"page":"910-921","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Gene mutations in hepatocellular adenomas"],"prefix":"10.1111","volume":"66","author":[{"given":"Marie B","family":"Raft","sequence":"first","affiliation":[{"name":"Department of Pathology Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ern\u00f6 N","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Pathology Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Vainer","sequence":"additional","affiliation":[{"name":"Department of Pathology Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,10,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.2930180112"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02667.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"crossref","first-page":"253\u2013261","DOI":"10.1155\/2013\/253261","article-title":"Pathological diagnosis of hepatocellular cellular adenoma according to the clinical context","volume":"2013","author":"Bioulac\u2010Sage P","year":"2013","journal-title":"Int. J. Hepatol."},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.02.032"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22995"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182653ece"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1272837"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031552"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23362"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610725200"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07475"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110283"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.07.018"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.36126"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.06.016"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21068"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000268406"},{"key":"e_1_2_5_20_1","doi-asserted-by":"crossref","first-page":"417323","DOI":"10.1155\/2013\/417323","article-title":"Value and limits of routine histology alone or combined with glutamine synthetase immunostaining in the diagnosis of hepatocellular adenoma subtypes on surgical specimens","volume":"2013","author":"Bioulac\u2010Sage P","year":"2013","journal-title":"Int. J. Hepatol."},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2013.04.008"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.10.003"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2008.01849.x"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21743"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0b013e318234abb4"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.03.005"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-0172(90)90055-K"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.114"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70262-9"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.02.004"},{"key":"e_1_2_5_31_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/PAI.0b013e31825d527f","article-title":"Utility of an immunohistochemical panel consisting of glypican\u20103, heat\u2010shock protein\u201070, and glutamine synthetase in the distinction of low\u2010grade hepatocellular carcinoma from hepatocellular adenoma","volume":"21","author":"Lagana SM","year":"2013","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2012.07.019"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2009.03343.x"},{"key":"e_1_2_5_34_1","article-title":"Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor","author":"Kakar S","year":"2013","journal-title":"Mod. Pathol."},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3218"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.12539","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.12539","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T09:36:54Z","timestamp":1695548214000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.12539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,30]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1111\/his.12539"],"URL":"https:\/\/doi.org\/10.1111\/his.12539","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,30]]},"assertion":[{"value":"2014-10-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}