{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T22:46:04Z","timestamp":1770417964123,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T00:00:00Z","timestamp":1570060800000},"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":[[2019,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Thymic carcinoma is rare and usually has a fatal outcome. Gene mutations in the epidermal growth factor receptor (EGFR) signalling pathway and <jats:italic>TP53<\/jats:italic> have not been well analysed in thymic carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We examined a large cohort of thymic carcinoma and thymoma type A\/B3 and looked for gene mutations in the <jats:italic>RAS<\/jats:italic> family, <jats:italic>EGFR<\/jats:italic>, <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>AKT1<\/jats:italic>, <jats:italic>BRAF<\/jats:italic> and <jats:italic>TP53<\/jats:italic>. Among 54 thymic carcinoma cases, <jats:italic>RAS<\/jats:italic> family mutations were detected in 10 cases, <jats:italic>EGFR<\/jats:italic> in two, <jats:italic>PIK3CA<\/jats:italic> in one, <jats:italic>AKT1<\/jats:italic> in one, <jats:italic>BRAF<\/jats:italic> in none and <jats:italic>TP53<\/jats:italic> in five. Among 33 thymoma type A\/B3 cases, <jats:italic>HRAS<\/jats:italic> gene mutation were found in one, <jats:italic>PIK3CA<\/jats:italic> in two and <jats:italic>AKT1<\/jats:italic> in one. All these mutations were those of missense type activating mutations. <jats:italic>RAS<\/jats:italic> family mutations were significantly more frequent in thymic carcinoma than in thymoma type A\/B3 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0461). A prognostic analysis focusing on thymic squamous cell carcinoma cases (<jats:italic>n<\/jats:italic>\u00a0=\u00a044) showed that the overall survival was significantly shorter in patients with EGFR pathway mutations (<jats:italic>n<\/jats:italic>\u00a0=\u00a09) than in those without in a univariate analysis (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0173). Subsequently, EGFR pathway mutations were selected as an independent factor for a poor overall survival in a multivariate analysis (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0389).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mutations in the EGFR pathway and <jats:italic>TP53<\/jats:italic> in thymic carcinoma may be frequent, and the EGFR pathway mutations may be associated with a poor prognosis in thymic squamous cell carcinoma patients. The therapeutic significance of gene mutations in thymic carcinoma should be further clarified.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13936","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T08:45:14Z","timestamp":1560156314000},"page":"755-766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A mutation analysis of the EGFR pathway genes, <i>RAS<\/i>, <i>EGFR<\/i>, <i>PIK3CA<\/i>, <i>AKT1<\/i> and <i>BRAF<\/i>, and <i>TP53<\/i> gene in thymic carcinoma and thymoma type A\/B3"],"prefix":"10.1111","volume":"75","author":[{"given":"Tadashi","family":"Sakane","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Nagoya City University Graduate School of Medical Sciences Nagoya Japan"},{"name":"Department of Oncology, Immunology and Surgery Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Murase","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuhiro","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Oncology, Immunology and Surgery Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosuke","family":"Saida","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Kariya Toyota General Hospital Kariya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yushi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Chest Surgery Toyota Memorial Hospital Toyota Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoichi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Immunology and Surgery Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6157-636X","authenticated-orcid":false,"given":"Hiroshi","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e3181f1f62d"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2007.11.004"},{"key":"e_1_2_7_4_1","volume-title":"WHO classification of tumours of lung, pleura, thymus and heart","author":"Travis WD","year":"2015"},{"key":"e_1_2_7_5_1","first-page":"743","article-title":"Abnormal thymocyte development and generation of autoreactive T cells in mixed and cortical thymomas","volume":"78","author":"Nenninger R","year":"1998","journal-title":"Lab. 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