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Updated: Jun 6, 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
Expression of Her-2 in carcinomas of the esophagus
Sebastian F Schoppmann1, Bettina Jesch, Julia Friedrich
1Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. sebastian.schoppmann@meduniwien.ac.at
Abstract:
The human epidermal growth factor receptor-2 gene (HER-2) encodes for a membrane-bound tyrosine kinase (Her-2), which is overexpressed in various human cancers. Her-2-targeted therapy has recently been shown to be beneficial for patients with advanced gastric cancer. Her-2 protein expression was investigated in 341 esophageal carcinomas [152 squamous cell carcinomas (SCC), 189 adenocarcinomas (AC)], 39 cases of Barrett mucosa, and 11 cases of squamous cell dysplasia. HER-2 gene amplification was assessed by colorimetric in-situ hybridization. Positive Her-2 status was found in 15.3% of ACs and 3.9% of SCCs. Positive Her-2-status was more common in dysplastic Barrett mucosas compared with nondysplastic ones (P=0.04). In 26% of the patients with ACs who had received neoadjuvant chemotherapy (n=39), the Her-2 status of pretherapeutic biopsies was different compared with subsequent surgical specimens. There was no statistically significant correlation between Her-2 status and patients' survival. Although Her-2 overexpression is rare in SCCs, it is found in 15.3% of ACs, where amplification of HER-2 gene and overexpression of Her-2 protein seem to be early events in carcinogenesis. The evaluation of Her-2 status in tumor biopsies and in particular in the context with possible alterations after neoadjuvant treatment can potentially lead to false Her-2-staging. Although Her-2-overexpression in esophageal cancer seems to have no influence on patients' survival, these subtypes of esophageal ACs have to be considered as targets for an anti-Her-2 therapy.
Insights
Human epidermal growth factor receptor-2 (HER-2) is overexpressed in esophageal adenocarcinomas (ACs) but rare in squamous cell carcinomas (SCCs). HER-2 status may change after neoadjuvant chemotherapy, impacting staging.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Human epidermal growth factor receptor-2 (HER-2) is a membrane-bound tyrosine kinase implicated in various cancers.
- HER-2 targeted therapy shows promise in advanced gastric cancer.
- HER-2 overexpression is a known oncogenic driver in several malignancies.
Purpose of the Study:
- To investigate HER-2 protein expression and gene amplification in esophageal carcinomas, Barrett mucosa, and squamous cell dysplasia.
- To determine the correlation between HER-2 status and clinicopathological features, including survival.
- To assess the impact of neoadjuvant chemotherapy on HER-2 status in esophageal adenocarcinoma.
Main Methods:
- HER-2 protein expression and gene amplification were assessed in 341 esophageal carcinomas (152 SCC, 189 AC), 39 Barrett mucosa cases, and 11 squamous cell dysplasia cases.
- Colorimetric in-situ hybridization was used to evaluate HER-2 gene amplification.
- HER-2 status was compared between pre- and post-neoadjuvant chemotherapy specimens.
Main Results:
- Positive HER-2 status was observed in 15.3% of ACs and 3.9% of SCCs.
- HER-2 positivity was more frequent in dysplastic Barrett mucosa than non-dysplastic types (P=0.04).
- In 26% of AC patients receiving neoadjuvant chemotherapy, HER-2 status differed between pre-treatment biopsies and surgical specimens. No significant correlation was found between HER-2 status and patient survival.
Conclusions:
- HER-2 overexpression is infrequent in esophageal squamous cell carcinoma but present in a notable subset of adenocarcinomas, suggesting early involvement in carcinogenesis.
- Altered HER-2 status post-neoadjuvant therapy can lead to inaccurate staging.
- Esophageal adenocarcinomas with HER-2 overexpression represent potential targets for anti-HER-2 therapies, despite no observed impact on survival in this study.
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