{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:48:30Z","timestamp":1782236910274,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,8,9]],"date-time":"2012-08-09T00:00:00Z","timestamp":1344470400000},"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":[[2012,11]]},"abstract":"<jats:p>Fassan M, Mastracci L, Grillo F, Zagonel V, Bruno S, Battaglia G, Pitto F, Nitti D, Celiento T, Zaninotto G, Fiocca R &amp; Rugge M \u2028(2012) <jats:italic>Histopathology<\/jats:italic>\u00a0<jats:bold>61,<\/jats:bold> 769\u2013776<\/jats:p><jats:p><jats:bold>Early HER2 dysregulation in gastric and oesophageal carcinogenesis<\/jats:bold><\/jats:p><jats:p><jats:bold>Aims:\u2002<\/jats:bold> To explore human epidermal growth factor receptor 2 (HER2) status in the histological phenotypes [metaplasia, intraepithelial neoplasia (IEN, i.e. dysplasia), and adenocarcinoma] involved in the morphogenesis of both intestinal\u2010type gastric cancer (GC) and Barrett\u2019s adenocarcinoma (BAc).<\/jats:p><jats:p><jats:bold>Methods and results:\u2002<\/jats:bold> A consecutive series of 275 samples of stomach and oesophagus tissue (representing the whole spectrum of the phenotypic changes involved in gastric and Barrett\u2019s carcinogenesis) was studied. HER2 status was assessed by applying two immunohistochemistry (IHC) protocols, using the antibodies 4B5 and CB11. Dual\u2010colour silver chromogenic <jats:italic>in\u2010situ<\/jats:italic> hybridization (SISH) was also performed on the same tissue samples. In both oesophageal and gastric samples, the rate of HER2 overexpression rose significantly from low\u2010grade to high\u2010grade IEN to adenocarcinoma (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001), with the two IHC protocols showing consistent staining (consistency 95%; <jats:italic>k<\/jats:italic>\u2003=\u20030.78; <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001). Intratumour heterogeneity was documented in both GC and BAc (using both IHC protocols). The rate of <jats:italic>HER2<\/jats:italic> amplification (using SISH) increased significantly along with IEN dedifferentiation (<jats:italic>P<\/jats:italic>\u2003&lt; 0.001). Neither native nor metaplastic mucosa samples (obtained from either stomach or oesophagus) ever showed <jats:italic>HER2<\/jats:italic> amplification. There was excellent agreement between <jats:italic>HER2<\/jats:italic> amplification and protein overexpression (both IHC protocols: SISH\/4B5\u2013\u2013consistency 97.8%, <jats:italic>k<\/jats:italic>\u2003=\u20030.89, <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001; SISH\/CB11\u2014consistency 97.8%, <jats:italic>k<\/jats:italic>\u2003=\u20030.91, <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001).<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> There is early involvement of HER2 dysregulation (amplification and protein overexpression) in both gastric (intestinal\u2010type) and Barrett\u2019s oncogenesis.<\/jats:p>","DOI":"10.1111\/j.1365-2559.2012.04272.x","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T15:48:59Z","timestamp":1331826539000},"page":"769-776","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Early HER2 dysregulation in gastric and oesophageal carcinogenesis"],"prefix":"10.1111","volume":"61","author":[{"given":"Matteo","family":"Fassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mastracci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Grillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorina","family":"Zagonel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Battaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pitto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donato","family":"Nitti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Celiento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Zaninotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Fiocca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Rugge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,9]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1590-8658(11)60593-8"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1590-8658(11)60588-4"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2006.040386"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.728"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2010.04277.x"},{"key":"e_1_2_9_7_2","article-title":"Indefinite for dysplasia in the stomach: the role of gastric mucosa atrophy","author":"Fassan M","year":"2012","journal-title":"Am. J. Clin. Pathol."},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2006.09.021"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2008.02094_9.x"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2009.03.022"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i48.5231"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25823"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61121-X"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2008.03028.x"},{"key":"e_1_2_9_15_2","first-page":"347","article-title":"Targeted therapy with trastuzumab in dysplasia and adenocarcinoma arising in Barrett\u2019s esophagus: a translational approach","volume":"54","author":"Villanacci V","year":"2008","journal-title":"Minerva Gastroenterol. Dietol."},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00517.x"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2010.03580.x"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03760.x"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2011.09.004"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.47"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2011.05.019"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.52"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03894.x"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.04012.x"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2010-0541-OA"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.04017.x"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2010.12.017"},{"key":"e_1_2_9_28_2","volume-title":"World Health Organization classification of tumours of the digestive system","author":"Bosman FT","year":"2010"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2010.02.016"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.144"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2011.089847"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2559.2012.04272.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2559.2012.04272.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T06:25:14Z","timestamp":1697351114000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2559.2012.04272.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,9]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1111\/j.1365-2559.2012.04272.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2559.2012.04272.x","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,9]]},"assertion":[{"value":"2012-08-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}