HER2 and EGFR Gene Copy Number Alterations Are Predominant in High‐Grade Salivary Mucoepidermoid Carcinoma

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.