HER2 expression and HER2 gene amplification in thymic epithelial tumors: a narrative review

Background and Objective Thymic epithelial tumors (TETs) are a rare group of neoplasms situated in the prevascular mediastinum. Due to their rarity and histological diversity, understanding their development is quite challenging, and their molecular profile is not well defined. Although advances in molecular profiling have improved our understanding of many solid cancers, TET remains poorly characterized. The human epidermal growth factor receptor 2 (HER2/ERBB2) has gained interest as a molecular target due to its role in oncogenesis and its therapeutic significance in various malignancies; however, its potential role in treating TET remains unclear. This review examines the expression patterns, gene amplification status, and clinical implications of HER2 in thymomas and thymic carcinomas, especially in the era of antibody-drug conjugates which target tumors with low HER2 expression. Methods PubMed, Embase and Web of Science research was conducted using the terms [HER2] OR [ERBB2] OR [ErbB2] OR [HER2/neu] OR [c-erB2] AND [thymic epithelial tumors], [HER2] OR [ERBB2] OR [ErbB2] OR [HER2/neu] OR [c-erB2] AND [thymoma], and [HER2] OR [ERBB2] OR [ErbB2] OR [HER2/neu] OR [c-erB2] AND [thymic carcinoma]. There were no restrictions on publication date. After analysis, nine articles met the research criteria. Key Content and Findings In one study, thymic carcinomas expressed HER2 frequently, with focal to strong membranous positivity in 8 of the 17 cases. In another, HER2 was expressed in 58.3% of cases with other members of the receptor family and signaling pathway ligands also demonstrating frequent expression. The immunohistochemical analysis revealed that the receptors epidermal growth factor receptor (EGFR) (33.3%), phosphorylated epidermal growth factor receptor (pEGFR) (33.3%), and human epidermal growth factor receptor 3 (HER3) (45.8%), along with the ligands transforming growth factor-α (TGF-α) (54.2%), amphiregulin (25.0%), and epiregulin (91.7%), were expressed in the tumor cells. Only one case showed HER2 gene amplification. In another study, HER2 expression was positive in only one case of thymic carcinoma (1/22), whereas there was no expression observed in any of the thymoma cases (0/22). In the other series, there were scarce or no cases with HER2 expression or gene amplification. Conclusions HER2 plays a still undefined role in TET, especially in thymic carcinoma. Although gene amplification is rare, protein expression is more frequent, suggesting potential for targeted therapy. Detailed molecular profiling and innovative research methods are essential to further explore the therapeutic potential of HER2 in these rare cancers.