Insights From Mutational and Transcriptomic Profiles in Epithelial-myoepithelial Carcinoma.

Abstract

Epithelial-myoepithelial carcinoma (EMC) is a rare malignant tumor of the salivary glands, often characterized by HRAS mutations. The present study aimed to better define the molecular and transcriptomic landscape of EMC and explore its relationship with other head and neck neoplasms, particularly basal cell adenoma (BCA). We retrospectively analyzed 14 EMC cases using histology, immunohistochemistry, and whole-exome capture RNA sequencing. HRAS mutations were identified in 57.0% (8/14) of EMC, predominantly at p.Gly61Arg. Additional mutations identified included PIK3CA , STAT5B , and NOTCH1 , as well as gene fusions such as HMGA2 :: WIF1 and FBXO32 :: PLAG1 . A comparative analysis with 54 RAS -mutated head and neck tumors revealed that HRAS mutations were not exclusive to EMC, as they were also found in benign entities such as BCAs. Transcriptomic profiling found that EMC and BCA shared significant gene expression similarities, clustering closely. Differential expression analysis found upregulation of GATA3 , CHI3L1 , GRIA2 , and MME in EMC, while BCAs had enrichment of Wnt-beta-catenin signaling. In contrast, EMCs had activation of the Ras-Raf-MAPK and PI3K-Akt pathways, supported by upregulation of E2F and G2-M checkpoint targets. Immunohistochemistry confirmed GATA3 positivity in HRAS -mutated EMCs. The frequent RAS mutations and overlapping transcriptomic profiles raise important diagnostic considerations and highlight the need for integrated molecular analyses to differentiate these entities. The EMCs displayed a recurrent HRAS mutation, also observed in other head and neck tumors, and were partially clustered with the cases of BCA, suggesting potential biological similarities.