HER2 and EGFR gene copy number alterations are predominant in high-grade salivary mucoepidermoid carcinoma irrespective of MAML2 fusion status

Takafumi Nakano, Hidetaka Yamamoto, Kazuki Hashimoto, Sadafumi Tamiya, Hideki Shiratsuchi, Torahiko Nakashima, Ken Ichi Nishiyama, Yuichiro Higaki, Shizuo Komune, Yoshinao Oda

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Pages (from-to)378-392
Number of pages15
JournalHistopathology
Volume63
Issue number3
DOIs
Publication statusPublished - Sep 1 2013

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology

Cite this