{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T02:03:18Z","timestamp":1760061798229,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,9,28]],"date-time":"2017-09-28T00:00:00Z","timestamp":1506556800000},"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":[[2017,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Oesophageal adenocarcinoma (<jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content>) tumorigenesis has been linked primarily to loss\u2010of\u2010function mutations in tumour suppressor genes. Knowledge of specific oncogenes that drive tumour progression, and their relationship to outcomes, is limited. High mobility group <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>\u2010hook 2 (<jats:italic><jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2<\/jats:italic>) has been reported to be amplified in a subset of <jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content>s, but the clinicopathological and prognostic implications of <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2 expression in <jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content> are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We performed <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2 immunohistochemistry and fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridization (<jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content>) in <jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content> to determine its clinicopathological and prognostic significance. Ninety\u2010one primary <jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content> resections without neoadjuvant treatment were identified and immunohistochemistry for <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2 was performed. The presence or absence of nuclear staining was evaluated and correlated with predetermined clinicopathological parameters and patient outcomes. A selected subset of tumours was subjected to <jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content> to identify alterations at the <jats:italic><jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2<\/jats:italic> locus. <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2 expression was present in 25 of 91 (27.4%) tumours. <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2\u2010expressing cells were present in solid, poorly differentiated areas of the tumours at the invasive front, or as single infiltrating cells. <jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content> showed that three to four copies of <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2 are frequently present in <jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content> irrespective of <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2 protein expression and that high level <jats:italic><jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2<\/jats:italic> amplification is a rare event. <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2 expression was associated with numerous adverse clinicopathological parameters, including higher T\u2010 and N\u2010stage, the presence of lymphovascular invasion and with a worse recurrence\u2010free and overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that <jats:italic><jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2<\/jats:italic> is regulated in <jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content> primarily through non\u2010chromosomal\u2010level alterations that lead to increased <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2 expression. <jats:styled-content style=\"fixed-case\">HMGA<\/jats:styled-content>2\u2010positive <jats:styled-content style=\"fixed-case\">EAC<\/jats:styled-content> correlates with adverse pathological features and worse patient outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13310","type":"journal-article","created":{"date-parts":[[2017,7,15]],"date-time":"2017-07-15T06:42:41Z","timestamp":1500100961000},"page":"909-917","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Prevalence and significance of <scp>HMGA<\/scp>2 expression in oesophageal adenocarcinoma"],"prefix":"10.1111","volume":"71","author":[{"given":"Jeffrey K","family":"Mito","sequence":"first","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agoston T","family":"Agoston","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Dal Cin","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5165-8142","authenticated-orcid":false,"given":"Amitabh","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,9,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60643-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji024"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21332"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv048"},{"key":"e_1_2_7_6_1","first-page":"1351","article-title":"P53 in esophageal adenocarcinoma: a critical reassessment of mutation frequency and identification of 72arg as the dominant allele","volume":"31","author":"Chung SM","year":"2007","journal-title":"Int. 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