{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T19:29:50Z","timestamp":1748892590268,"version":"3.40.5"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81702372"],"award-info":[{"award-number":["81702372"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012543","name":"Shanghai Science and Technology Development Foundation","doi-asserted-by":"publisher","award":["19MC1911000"],"award-info":[{"award-number":["19MC1911000"]}],"id":[{"id":"10.13039\/100012543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aimed to determine the frequency of <jats:italic>mouse double minute 2<\/jats:italic> (<jats:italic>MDM2<\/jats:italic>) amplification in oesophageal squamous cell carcinomas (ESCC) and to clarify its prognostic significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We investigated <jats:italic>MDM2<\/jats:italic> amplification on tissue microarrays using fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridisation and analysed its correlations with clinicopathological features and outcomes in 515 Chinese ESCC patients. <jats:italic>MDM2<\/jats:italic> amplifications were found in 37 of 515 ESCC patients (7.2%). They were significantly negatively correlated with tumour size (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.045), disease progression (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.002) and death (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003). Univariate analysis showed that the following clinicopathological factors were associated with disease\u2010free survival (DFS) and overall survival (OS): differentiation (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.025 for DFS and <jats:italic>P\u00a0=\u00a0<\/jats:italic>0.061 for OS), vessel invasion (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.001 and <jats:italic>P\u00a0=\u00a0<\/jats:italic>0.002), nerve invasion (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.009 and <jats:italic>P\u00a0=\u00a0<\/jats:italic>0.001), clinical stage (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 and <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001) and <jats:italic>MDM2<\/jats:italic> amplification (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.012 and <jats:italic>P\u00a0=\u00a0<\/jats:italic>0.014). Multivariate Cox regression analysis showed that <jats:italic>MDM2<\/jats:italic> amplification was an independent prognostic factor for improved outcomes (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.023 for DFS, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.027 for OS) and the clinical stage was an independent prognostic factor for poor outcomes (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). When survival analyses were conducted at different clinical stages, <jats:italic>MDM2<\/jats:italic> amplification was associated with longer DFS and OS in stages I\u2013II ESCC (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003 for DFS and <jats:italic>P\u00a0=\u00a0<\/jats:italic>0.003 for OS), but there was no significant survival difference in stages III\u2013IVa ESCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>MDM2<\/jats:italic> amplification was significantly correlated with an improved patient outcome, especially in stage I and II disease, and was verified as an independent prognostic factor in our patients. Therefore, <jats:italic>MDM2<\/jats:italic> amplification may be a potential biomarker for risk stratification of the lower stages of ESCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14208","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T20:54:41Z","timestamp":1594500881000},"page":"963-973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>Mouse double minute 2<\/i> amplification in oesophageal squamous cell carcinoma is associated with better outcome"],"prefix":"10.1111","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0203-0356","authenticated-orcid":false,"given":"Dongxian","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Pathology Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingli","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pathology Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Evidence\u2010based Medicine Fudan University Shanghai China"},{"name":"Center for Data Management and Statistics Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9156-2305","authenticated-orcid":false,"given":"Yingyong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pathology Zhongshan Hospital Fudan University Shanghai China"},{"name":"Department of Pathology School of Basic Medical Sciences and Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2018.01.01"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31462-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-083115-022413"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2006.06.007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08822"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20805"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13176"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01535205"},{"key":"e_1_2_7_11_1","first-page":"627","article-title":"Emerging role of MDM2 as target for anti\u2010cancer therapy: a review","volume":"46","author":"Shaikh MF","year":"2016","journal-title":"Ann. 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