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Updated: Jun 1, 2026

Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Human epidermal growth factor receptor 2 (HER2) in salivary gland carcinomas
Till Sebastian Clauditz1, Maren Reiff, Linn Gravert
1Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. t.clauditz@uke.de
Background:
HER2 is a target for antibody-based treatment of breast and gastric carcinoma which is highly successful in advanced disease as well as in the adjuvant setting. To determine the potential applicability of such therapies, salivary gland tumours were analysed for HER2 overexpression/amplification in this study.
Methods:
A tissue microarray (TMA) was constructed from 994 carcinomas and 205 adenomas of the salivary gland. Slides were analysed for HER2 overexpression and gene amplification using FDA approved reagents for immunohistochemistry (IHC; Hercep-Test; Dako) and fluorescence in situ hybridisation (FISH; PathVysion; Vysis-Abbott).
Results:
HER2 was found overexpressed in 39 of 915 (4.26%) and amplified in nine of 915 interpretable salivary gland carcinomas (0.98%). HER2 overexpression was mostly found in salivary duct carcinoma. All other entities were mainly HER2 negative. HER2 was overexpressed in 34 of 319 (10.65%) mucoepidermoid carcinomas, one of 170 (0.59%) acinic cell adenocarcinomas and three of 14 (21.43%) salivary duct carcinomas. HER2 amplification was seen in three of 294 (1.01%) mucoepidermoid carcinomas, three of 14 (21.43%) salivary duct carcinomas, one of 81 (1.23%) adenocarcinomas (NOS), one of 12 (8.33%) cystadenocarcinomas and one of 19 (2.08%) myoepithelial carcinomas. HER2 amplification was found in seven of 39 immunohistochemically HER2 positive (2+ and 3+) tumours (17.95%) but in only two of 849 (0.24%) IHC negative tumours (p < 0.0001). No amplification/overexpression was found in adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous low grade carcinoma, basal cell carcinoma, myoepithelial carcinoma, cystadenocarcinoma and oncocytic carcinoma.
Conclusion:
HER2 overexpression caused by gene amplification was observed in about 20% of patients with salivary duct cancers but was rare in salivary adenomas and other carcinomas. Therefore, anti-HER2 therapy may represent a therapeutic option only in a small subgroup of salivary gland tumours.
Insights
HER2 overexpression and amplification are rare in most salivary gland tumors, but occur in about 20% of salivary duct cancers. This suggests anti-HER2 therapy may benefit a small subset of patients.
Area of Science:
- Oncology
- Molecular Pathology
Background:
- HER2 is a validated target for antibody-based therapies in advanced and adjuvant breast and gastric carcinomas.
- Investigating HER2 expression in salivary gland tumors is crucial for assessing potential therapeutic applications.
Purpose of the Study:
- To analyze the prevalence of HER2 (Human Epidermal growth factor Receptor 2) overexpression and gene amplification in various types of salivary gland tumors.
- To determine if HER2-targeted therapies could be a viable treatment option for specific salivary gland cancer subtypes.
Main Methods:
- A tissue microarray (TMA) comprising 994 carcinomas and 205 adenomas of the salivary gland was constructed.
- HER2 overexpression was assessed using immunohistochemistry (IHC), and gene amplification was evaluated via fluorescence in situ hybridization (FISH), utilizing FDA-approved reagents.
Main Results:
- HER2 overexpression was detected in 4.26% of salivary gland carcinomas, with amplification in 0.98%.
- Salivary duct carcinoma showed the highest rates, with HER2 overexpression in 21.43% and amplification in 21.43% of cases.
- HER2 amplification was significantly more common in IHC-positive tumors (17.95%) compared to IHC-negative tumors (0.24%).
Conclusions:
- HER2 overexpression due to gene amplification occurs in approximately 20% of salivary duct cancers.
- HER2 overexpression and amplification are infrequent in salivary adenomas and other salivary gland carcinomas.
- Anti-HER2 therapy might be a potential treatment option for a limited subgroup of patients with specific salivary gland tumors.
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