title: HER2 and EGFR gene copy number alterations are predominant in high-grade salivary mucoepidermoid carcinoma irrespective of MAML2 fusion status.
abstract: OBJECTIVE
  In this study, we aimed to investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma (MEC).
  
  
  RESULTS
  In 31 cases, we examined the MAML2 fusion status using reverse transcriptase-polymerase chain reaction, and HER2 and EGFR status using immunohistochemistry and chromogenic in-situ hybridization. MAML2 fusions were detected in 15 (57.7%) of 26 MECs analysed, including 11 of 16 (68.8%) low-grade, two of four (50%) intermediate-grade and two of six (33.3%) high-grade MECs. HER2 gene amplification and an increased EGFR gene copy number (with balanced chromosome 7 high-polysomy) were each detected in four of 28 (14.3%) MECs analysed. Irrespective of MAML2 fusion status, all seven high-grade MECs had an increased gene copy number of either HER2 or EGFR, in a mutually exclusive manner, whereas such abnormalities were extremely rare in low- and intermediate-grade MEC.
  
  
  CONCLUSIONS
  These results suggest that HER2 or EGFR gene abnormality could play an important role in the development of high-grade MEC, and also in the progression from MAML2 fusion-positive low-/intermediate-grade to high-grade in a subset of MEC. Furthermore, we suggest that high-grade MEC comprises a heterogeneous group of tumours in terms of molecular pathogenesis, in particular MAML2 fusion status.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Otolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakano
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Sadafumi
authors.initials: S
authors.lastname: Tamiya
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiratsuchi
authors.forename: Torahiko
authors.initials: T
authors.lastname: Nakashima
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Higaki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Komune
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D018277:Carcinoma, Mucoepidermoid / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D050939:Gene Fusion; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics*; D010307:Parotid Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012189:Retrospective Studies; D012468:Salivary Gland Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D013365:Submandibular Gland Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D009687:Nuclear Proteins; D048493:Proto-Oncogene Proteins B-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; C471297:MAML2 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human
keywords: HER2; MAML2 fusion; chromogenic in-situ hybridization; epidermal growth factor receptor; mucoepidermoid carcinoma