HER2 and EGFR Gene Copy Number Alterations Are Predominant in High‐Grade Salivary Mucoepidermoid Carcinoma. (23rd August 2013)

• Record Type: Journal Article
• Authors: Nakano, Takafumi; Yamamoto, Hidetaka; Hashimoto, Kazuki; Yasumatsu, Ryuji; Nakashima, Torahiko; Oda, Yoshinao; Komune, Shizuo
• Is Part Of: Otolaryngology--head and neck surgery. Volume 149(2013)Supplement 2
• Page Start: P174
• Page End: P174
• Publication Date: 2013-08-23
• Subjects: Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599813496044a97
• Languages: English
• ISSNs: 0194-5998

Abstract

Abstract : Objectives: Investigate the molecular mechanisms underlying the development of mucoepidermoid carcinoma (MEC). Methods: We investigated the MAML2 fusion status using reverse transcriptase‐polymerase chain reaction, and HER2 and epidermal growth factor receptor (EGFR) status using immunohistochemistry and chromogenic in‐situ hybridization in 31 cases. Results: MAML2 fusions were detected in 57.7% MECs analyzed, including 68.8% low‐grade, 50% intermediate‐grade and 33.3% high‐grade MECs. HER2 gene amplification was present in 14.3% MECs analyzed, including 25% intermediate‐grade and 42.9% high‐grade MECs. An increased EGFR gene copy number was detected in 14.3% MECs analyzed, and was correlated with both high tumor grade (P=0.0017) and worse outcome ( P < 0.0001). Irrespective of MAML2 fusion status, all of 7 high‐grade MECs had an increased gene copy number of either HER2 or EGFR gene 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 may 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 consists of a heterogeneous group of tumors in terms of molecular pathogenesis in particular MAML2 fusion status.