{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:58:38Z","timestamp":1780473518129,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,7,16]],"date-time":"2013-07-16T00:00:00Z","timestamp":1373932800000},"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":[[2013,9]]},"abstract":"Aims<\/jats:title>In this study, we aimed to investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma (MEC<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods and results<\/jats:title>In 31 cases, we examined the MAML<\/jats:styled-content>2<\/jats:italic> fusion status using reverse transcriptase\u2013polymerase chain reaction, and HER<\/jats:styled-content>2 and EGFR<\/jats:styled-content> status using immunohistochemistry and chromogenic in\u2010situ<\/jats:italic> hybridization. MAML<\/jats:styled-content>2<\/jats:italic> fusions were detected in 15 (57.7%) of 26 MEC<\/jats:styled-content>s analysed, including 11 of 16 (68.8%) low\u2010grade, two of four (50%) intermediate\u2010grade and two of six (33.3%) high\u2010grade MEC<\/jats:styled-content>s. HER<\/jats:styled-content>2<\/jats:italic> gene amplification and an increased EGFR<\/jats:styled-content><\/jats:italic> gene copy number (with balanced chromosome 7 high\u2010polysomy) were each detected in four of 28 (14.3%) MEC<\/jats:styled-content>s analysed. Irrespective of MAML<\/jats:styled-content>2<\/jats:italic> fusion status, all seven high\u2010grade MEC<\/jats:styled-content>s had an increased gene copy number of either HER<\/jats:styled-content>2<\/jats:italic> or EGFR<\/jats:styled-content>,<\/jats:italic> in a mutually exclusive manner, whereas such abnormalities were extremely rare in low\u2010 and intermediate\u2010grade MEC<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>These results suggest that HER<\/jats:styled-content>2<\/jats:italic> or EGFR<\/jats:styled-content><\/jats:italic> gene abnormality could play an important role in the development of high\u2010grade MEC<\/jats:styled-content>, and also in the progression from MAML<\/jats:styled-content>2<\/jats:italic> fusion\u2010positive low\u2010\/intermediate\u2010grade to high\u2010grade in a subset of MEC<\/jats:styled-content>. Furthermore, we suggest that high\u2010grade MEC<\/jats:styled-content> comprises a heterogeneous group of tumours in terms of molecular pathogenesis, in particular MAML<\/jats:styled-content>2<\/jats:italic> fusion status.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12183","type":"journal-article","created":{"date-parts":[[2013,5,6]],"date-time":"2013-05-06T15:11:03Z","timestamp":1367853063000},"page":"378-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["HER<\/scp>2<\/i> and EGFR<\/scp><\/i> gene copy number alterations are predominant in high\u2010grade salivary mucoepidermoid carcinoma irrespective of MAML<\/scp>2<\/i> fusion status"],"prefix":"10.1111","volume":"63","author":[{"given":"Takafumi","family":"Nakano","sequence":"first","affiliation":[{"name":"Department of Anatomic Pathology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Department of Otolaryngology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Department of Otolaryngology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Department of Otorhinolaryngology and Head and Neck Surgery Kyushu Kouseinenkin Hospital Kitakyushu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadafumi","family":"Tamiya","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"},{"name":"Department of Pathology Kitakyushu Municipal Medical Center Kitakyushu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Shiratsuchi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torahiko","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken\u2010ichi","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Pathology National Kyushu Cancer Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Higaki","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery National Kyushu Cancer Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Komune","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinao","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Graduate School of Medical Sciences Kyushu University Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-09-0638"},{"key":"e_1_2_7_3_1","first-page":"173","volume-title":"AFIP atlas of tumor pathology, Series 4, Fascicle 9. Tumors of the salivary glands","author":"Ellis GL","year":"2008"},{"key":"e_1_2_7_4_1","first-page":"219","volume-title":"World Health Organization classification of tumours. Pathology and genetics of head and neck tumours","author":"Goode RK","year":"2005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200107000-00001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26697"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181de3021"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2006.11.045"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23825"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19980401)82:7<1217::AID-CNCR2>3.0.CO;2-C"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.126"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20719"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2376"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20306"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2008.03.012"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20458"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2008.03159.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2011.08.006"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2009.00770.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2006.00421.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605788"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e31819667a3"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604875"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0913"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-3284-3-11"},{"key":"e_1_2_7_26_1","first-page":"5675","article-title":"Amplification and overexpression of HER\u20102\/neu in carcinomas of the salivary gland: correlation with poor prognosis","volume":"54","author":"Press MF","year":"1994","journal-title":"Cancer Res."},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.3025"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.5858\/2000-124-0836-RGMISG"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000201)88:3<518::AID-CNCR4>3.0.CO;2-W"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/501736"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.2775"},{"key":"e_1_2_7_32_1","first-page":"435","article-title":"Epidermal growth factor receptor and human epidermal growth receptor 2 expression in parotid mucoepidermoid carcinoma: possible implications for targeted therapy","volume":"19","author":"Shang J","year":"2008","journal-title":"Oncol. Rep."},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318205df36"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2011.02679.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-3338"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2009.00320.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20522"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(94)90001-9"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(90)90250-E"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.113"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(03)00097-6"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.8612"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.12183","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.12183","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T23:23:51Z","timestamp":1696375431000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.12183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,16]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1111\/his.12183"],"URL":"https:\/\/doi.org\/10.1111\/his.12183","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,16]]},"assertion":[{"value":"2013-01-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}