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HER 2 and EGFR gene copy number alterations are predominant in high‐grade salivary mucoepidermoid carcinoma irrespective of MAML 2 fusion status
Author(s) -
Nakano Takafumi,
Yamamoto Hidetaka,
Hashimoto Kazuki,
Tamiya Sadafumi,
Shiratsuchi Hideki,
Nakashima Torahiko,
Nishiyama Kenichi,
Higaki Yuichiro,
Komune Shizuo,
Oda Yoshinao
Publication year - 2013
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12183
Subject(s) - polysomy , mucoepidermoid carcinoma , fluorescence in situ hybridization , gene dosage , fusion gene , gene duplication , immunohistochemistry , biology , gene , microbiology and biotechnology , cancer research , medicine , carcinoma , chromosome , genetics , gene expression , immunology
Aims In this study, we aimed to investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma ( MEC ). Methods and results In 31 cases, we examined the MAML 2 fusion status using reverse transcriptase–polymerase chain reaction, and HER 2 and EGFR status using immunohistochemistry and chromogenic in‐situ hybridization. MAML 2 fusions were detected in 15 (57.7%) of 26 MEC s analysed, including 11 of 16 (68.8%) low‐grade, two of four (50%) intermediate‐grade and two of six (33.3%) high‐grade MEC s. HER 2 gene amplification and an increased EGFR gene copy number (with balanced chromosome 7 high‐polysomy) were each detected in four of 28 (14.3%) MEC s analysed. Irrespective of MAML 2 fusion status, all seven high‐grade MEC s had an increased gene copy number of either HER 2 or EGFR , in a mutually exclusive manner, whereas such abnormalities were extremely rare in low‐ and intermediate‐grade MEC . Conclusions These results suggest that HER 2 or EGFR gene abnormality could play an important role in the development of high‐grade MEC , and also in the progression from MAML 2 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 MAML 2 fusion status.