{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:48:34Z","timestamp":1784900914127,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,20]],"date-time":"2020-09-20T00:00:00Z","timestamp":1600560000000},"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":[[2021,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study was performed to elucidate the clinicopathological characteristics, genetic alterations and therapeutic targets of primary malignant melanoma of the oesophagus (PMME).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>The clinicopathology and molecular pathology of 13 PMME cases and 10 skin malignant melanoma (SKMM) cases were analysed with next\u2010generation sequencing (NGS) and immunohistochemistry. The 3\u2010year overall survival rate and the median survival time for PMME patients were 23.1% and 11.9\u00a0months, respectively. Three (23.1%) and eight (61.5%) PMME cases showed a papillary structure and lymph node metastasis, respectively. DNA and RNA hybridization capture\u2010based NGS analysis revealed that <jats:italic>NF1<\/jats:italic> was the most frequently mutated gene (30%) in 10 of the PMME cases. Other mutations detected in PMME included <jats:italic>SF3B1<\/jats:italic> (20%), <jats:italic>KRAS<\/jats:italic> (10%), <jats:italic>BRCA2<\/jats:italic> (10%), <jats:italic>KIT<\/jats:italic> (10%) and <jats:italic>TP53<\/jats:italic> (10%) mutations. Commonly detected <jats:italic>BRAF<\/jats:italic> mutations in SKMM were not detected in PMME. Immunohistochemistry and mutation status were concordant between p53\/c\u2010Kit and <jats:italic>TP53<\/jats:italic>\/<jats:italic>KIT<\/jats:italic>, respectively. Focal expression of programmed death\u2010ligand 1 was observed in one PMME sample. The tumour mutation burden in PMME was significantly lower than that in SKMM (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.030). No PMME case showed high microsatellite instability. RNA sequencing revealed a distinctive pattern with respect to RNA expression. T\u2010cell co\u2010stimulation differed between PMME and SKMM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The RAS\u2013mitogen\u2010activated protein kinase pathway is one of the main pathways involved in PMME. The genetic profile of PMME was similar to that of mucosal\/acral melanoma, but differed from the SKMM profile. A subset of PMMEs may contain actionable mutations. Immunotherapy seemed to be less effective for most PMMEs in this series.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14210","type":"journal-article","created":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T05:28:57Z","timestamp":1594531737000},"page":"240-251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Comprehensive clinicopathological and molecular analysis of primary malignant melanoma of the oesophagus"],"prefix":"10.1111","volume":"78","author":[{"given":"Sho","family":"Tsuyama","sequence":"first","affiliation":[{"name":"Department of Human Pathology Juntendo University, Graduate School of Medicine Tokyo 113\u20108421 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kohsaka","sequence":"additional","affiliation":[{"name":"Division of Cellular Signaling National Cancer Center Research Institute Tokyo 104\u20100045 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-9370","authenticated-orcid":false,"given":"Takuo","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Human Pathology Juntendo University, Graduate School of Medicine Tokyo 113\u20108421 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Suehara","sequence":"additional","affiliation":[{"name":"Intractable Disease Research Center Juntendo University, Graduate School of Medicine Tokyo 113\u20108421 Japan"},{"name":"Department of Orthopaedic Surgery Juntendo University School of Medicine Tokyo 113\u20108421 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Esophageal and Gastroenterological Surgery Juntendo University School of Medicine Tokyo 113\u20108421 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kajiyama","sequence":"additional","affiliation":[{"name":"Department of Esophageal and Gastroenterological Surgery Juntendo University School of Medicine Tokyo 113\u20108421 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Tsurumaru","sequence":"additional","affiliation":[{"name":"Department of Esophageal and Gastroenterological Surgery Juntendo University School of Medicine Tokyo 113\u20108421 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Ueno","sequence":"additional","affiliation":[{"name":"Division of Cellular Signaling National Cancer Center Research Institute Tokyo 104\u20100045 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Mano","sequence":"additional","affiliation":[{"name":"Division of Cellular Signaling National Cancer Center Research Institute Tokyo 104\u20100045 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Human Pathology Juntendo University, Graduate School of Medicine Tokyo 113\u20108421 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9690-8440","authenticated-orcid":false,"given":"Tsuyoshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Human Pathology Juntendo University, Graduate School of Medicine Tokyo 113\u20108421 Japan"},{"name":"Intractable Disease Research Center Juntendo University, Graduate School of Medicine Tokyo 113\u20108421 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5213"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e32831ef262"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10388-019-00674-z"},{"key":"e_1_2_9_5_1","first-page":"343","article-title":"Ein Fall von primarem Melanom des Osopagus","volume":"5","author":"Bauer EH","year":"1906","journal-title":"Arb. 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