{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:34:09Z","timestamp":1788449649154,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,4]],"date-time":"2021-04-04T00:00:00Z","timestamp":1617494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Myunggok Research Fund","award":["2017"],"award-info":[{"award-number":["2017"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1C1B5076001"],"award-info":[{"award-number":["NRF-2017R1C1B5076001"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is a lethal and clinically heterogeneous disease with a limited benefit from human epidermal growth factor receptor 2 (HER2)-targeted therapy. Recently, some studies have addressed the antitumoral effect of novel anti-HER2 drugs in HER2 low-expressing tumors. However, there have been few studies on the significance of low HER2 expression and genetic heterogeneity in PDAC. Using immunohistochemistry and dual-color silver-enhanced in situ hybridization based on the Trastuzumab for a gastric cancer scoring scheme, we evaluated HER2 protein expression, gene amplification, and genetic heterogeneity in three groups (HER2-neg, HER2-low, HER2-pos) of 55 patients. Among the 55 cases, 41.8% (23\/55) showed HER2 expression of any intensity. HER2 amplification independent of HER2 expression was 25.5% (14\/55). Patients in both these groups had a shorter overall survival than did patients in the HER2-neg group. HER2 genetic heterogeneity was identified in 37 (70.9%) of the 55 cases, mainly in HER2-neg and HER2-low groups. HER2 genetic heterogeneity significantly correlated with worse survival in the HER2-low and HER2-neg groups of PDAC. These findings support the hypothesis that low-level HER2 expression and heterogeneity have significant clinical implications in PDAC. HER2 heterogeneity might indicate the best strategies of combination therapies to prevent the development of subdominant clones with resistance potential.<\/jats:p>","DOI":"10.3390\/diagnostics11040653","type":"journal-article","created":{"date-parts":[[2021,4,5]],"date-time":"2021-04-05T11:48:29Z","timestamp":1617623309000},"page":"653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Prognostic Impact of HER2 Genetic and Protein Expression in Pancreatic Carcinoma\u2014HER2 Protein and Gene in Pancreatic Cancer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4564-7014","authenticated-orcid":false,"given":"Song-Hee","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pathology, Dong-A University College of Medicine, Busan 49201, Korea"},{"name":"Myunggok Medical Research Institute, Konyang University, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-6776","authenticated-orcid":false,"given":"Ki Hyun","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, Konyang University College of Medicine, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-9018","authenticated-orcid":false,"given":"Ah-Young","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam-si 13496, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.4143\/crt.2019.139","article-title":"Prediction of cancer incidence and mortality in Korea, 2019","volume":"51","author":"Jung","year":"2019","journal-title":"Cancer Res. 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