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HER2 Heterogeneity in Gastroesophageal Cancer Detected by Testing Biopsy and Resection Specimens
Ladan Fazlollahi, Helen E Remotti, Alina Iuga
1From the Department of Pathology and Cell Biology, Columbia University Medical Center, New York Presbyterian Hospital, New York.
Context:
- In advanced gastric, esophageal, and gastroesophageal junction adenocarcinomas (GE-GEJ-AC) that overexpress ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2), anti-HER2 monoclonal antibody therapy confers survival benefit. To select patients for treatment, HER2 expression and gene amplification are evaluated by immunohistochemistry (IHC) and in situ hybridization.
Objective:
- To determine whether GE-GEJ-AC tested for HER2 on biopsy specimens of a primary tumor show different IHC scores and/or HER2 amplification by in situ hybridization in matched resection specimens, potentially changing therapy eligibility.
Design:
- Immunohistochemistry and silver in situ hybridization were performed in biopsy and/or resection specimens from 100 patients. HER2 testing was performed in matched resection and biopsy specimens of 15 cases to determine whether GE-GEJ-AC with IHC scores of 0, 1+, and 2+ in biopsy and resection specimens had different IHC and silver in situ hybridization results.
Results:
- The IHC 3+ cases showed HER2 amplification in 4 of 5 cases (80%), and IHC scores of 0, 1+, and 2+ showed 3.5%, 14.3%, and 23.5% HER2 amplification by silver in situ hybridization. Among the 15 paired biopsy and resection specimens, 9 (60%) had at least pT2 stage GE-GEJ-AC with HER2 IHC scores of 0, 1+, or 2+ in the biopsy, and 2 of those 9 cases (22%) had IHC 3+ and HER2 amplification by silver in situ hybridization on the resection specimen.
Conclusions:
- Our data suggest that HER2 testing should be repeated on resection specimens of GE-GEJ-AC with HER2 IHC scores of negative (0 and 1+) or equivocal (2+) and in situ hybridization amplification negative biopsy specimen results to evaluate for HER2 heterogeneity when patients are being considered for anti-HER2 therapy.
Insights
HER2 testing on biopsy specimens may not reflect resection specimens in GE-GEJ-AC. Repeat testing on resection samples for HER2 (human epidermal growth factor receptor 2) is recommended for patients with negative or equivocal biopsy results considered for anti-HER2 therapy.
Area of Science:
- Oncology
- Molecular Diagnostics
- Gastrointestinal Cancer Research
Background:
- Advanced gastric, esophageal, and gastroesophageal junction adenocarcinomas (GE-GEJ-AC) benefit from anti-HER2 therapy.
- HER2 (human epidermal growth factor receptor 2) overexpression and gene amplification are key selection criteria.
- Immunohistochemistry (IHC) and in situ hybridization (ISH) are standard HER2 testing methods.
Purpose of the Study:
- To compare HER2 expression and amplification results between biopsy and matched resection specimens in GE-GEJ-AC.
- To assess the potential impact of discrepancies on anti-HER2 therapy eligibility.
- To investigate HER2 heterogeneity in GE-GEJ-AC.
Main Methods:
- 100 patients with GE-GEJ-AC underwent HER2 testing (IHC and silver ISH) on biopsy and/or resection specimens.
- 15 cases with matched biopsy and resection specimens were analyzed for HER2 status.
- Analysis focused on cases with low (0, 1+) or equivocal (2+) IHC scores on biopsy.
Main Results:
- HER2 amplification was observed in 80% of IHC 3+ cases.
- Among IHC 0, 1+, and 2+ cases, HER2 amplification rates were 3.5%, 14.3%, and 23.5% respectively.
- In 22% of matched cases with initially negative/equivocal biopsy results, resection specimens showed HER2 IHC 3+ and amplification.
Conclusions:
- HER2 testing discrepancies between biopsy and resection specimens can occur in GE-GEJ-AC.
- Repeat HER2 testing on resection specimens is crucial for cases with negative/equivocal biopsy results.
- This reassessment helps identify HER2 heterogeneity and optimize patient selection for anti-HER2 therapy.
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