Related Experiment Video
Updated: Jan 17, 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
Analysis of Human Epidermal Growth Factor Receptor 2 (HER2) Heterogeneity at the Protein and Gene Levels in
Ekaterina Menshikova1, Kristin Deeb1, Elizabeth M Genega1
1Department of Pathology and Laboratory Medicine, Emory University Hospital, Emory University School of Medicine, Atlanta, Georgia.
Abstract:
Targeted therapy directed against human epidermal growth factor receptor 2 (HER2) has shown promising results in HER2-positive endometrial cancer. Recent limited data suggest significant intratumoral heterogeneity in HER2 expression in serous carcinomas. We aimed to evaluate HER2 heterogeneity at the protein and gene levels and the impact of variable definitions in endometrial carcinomas including nonserous subtypes. We retrospectively identified biopsies and surgical specimens with available HER2 immunohistochemical (IHC) stains and fluorescence in situ hybridization (FISH) results. IHC stains and FISH data were reevaluated to assess variability in the HER2 protein expression and gene amplification. The overall HER2-positivity rate was 31% using the endometrial criteria, and 42.6% by the gastric criteria. Heterogeneous IHC staining was observed in 45.7% of tumors, predominating in 2+/3+ scores (P < .001). Re-evaluation of FISH revealed a 31% rate of heterogeneous gene amplification. Our study demonstrates a high frequency of HER2 heterogeneity at both the protein and the gene levels. Further studies on HER2 heterogeneity and treatment response are warranted for refining standardized testing and reporting algorithms.
Insights
Human epidermal growth factor receptor 2 (HER2) heterogeneity is common in endometrial cancer at both protein and gene levels. This finding impacts HER2 testing and treatment response, requiring further study for standardized algorithms.
Area of Science:
- Oncology
- Molecular Pathology
- Genetics
Background:
- Targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive endometrial cancer shows promise.
- Limited data suggest intratumoral HER2 expression heterogeneity in serous carcinomas.
Purpose of the Study:
- Evaluate HER2 heterogeneity at protein and gene levels in endometrial carcinomas.
- Assess the impact of variable HER2 definitions, including nonserous subtypes.
- Investigate HER2 variability in protein expression and gene amplification.
Main Methods:
- Retrospective analysis of endometrial biopsies and surgical specimens.
- Reevaluation of HER2 immunohistochemical (IHC) stains and fluorescence in situ hybridization (FISH) data.
- Assessment of HER2 protein expression and gene amplification variability.
Main Results:
- Overall HER2-positivity rates varied: 31% (endometrial criteria) vs. 42.6% (gastric criteria).
- Heterogeneous IHC staining observed in 45.7% of tumors, predominantly in 2+/3+ scores.
- Re-evaluation of FISH revealed a 31% rate of heterogeneous gene amplification.
Conclusions:
- High frequency of HER2 heterogeneity demonstrated at both protein and gene levels in endometrial carcinomas.
- Further studies are warranted on HER2 heterogeneity and treatment response.
- Refining standardized testing and reporting algorithms for HER2 is necessary.
