Related Experiment Video
Updated: Sep 20, 2025
Author Spotlight: FISH as a Tool for Precise Gene Amplification Assessment in Cancer Specimens
Published on: July 12, 2024
Characteristics of HER2 Gene Amplification by Fluorescence In Situ Hybridization in Endometrial Serous Carcinoma
1From the Department of Pathology, Yale University, New Haven, Connecticut.
Context.—:
Targeted anti-human epidermal growth factor receptor 2 (HER2) therapy has recently become the standard for advanced-stage and recurrent HER2-positive endometrial serous carcinoma (ESC) in the United States, and an endometrial carcinoma-specific HER2 testing algorithm has been proposed. However, comprehensive studies on the specific features of HER2 gene amplification in these tumors are lacking.
Objective.—:
To evaluate the characteristics of HER2 amplification in ESC in the context of breast and gastric HER2 fluorescence in situ hybridization (FISH) guidelines.
Design.—:
Ninety-four ESCs with available HER2 immunohistochemistry (IHC) and FISH were included. HER2 IHC was scored according to the proposed endometrial carcinoma-specific algorithm and FISH was evaluated by using the 2018 ESC clinical trial criteria, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2016 gastric criteria, and ASCO/CAP 2013 and 2018 breast criteria.
Results.—:
Most tumors (90.4%; 85 of 94) had a 2+ HER2 IHC score. Polysomy of chromosome 17 was present in 16% (15 of 94) and monosomy 17 was seen in 2% (2 of 94) of tumors. HER2 FISH interpretation per the clinical trial criteria (HER2/CEP17 ratio ≥ 2.0) showed 99% concordance with the current gastric and breast HER2 FISH interpretations.
Conclusions.—:
Our results support the clinical trial criteria for HER2 FISH in ESC with a modification to include HER2 IHC 2+ and HER2/CEP17 ratio less than 2.0 and average HER2 copy number of 6.0 or greater in the HER2-positive category. Future prospective clinical investigations are necessary to assess the correlation between specific HER2 FISH result categories and therapeutic response.
Insights
HER2 testing in endometrial serous carcinoma (ESC) shows high concordance with breast and gastric guidelines. A modified approach including specific HER2 IHC and FISH criteria is proposed for improved HER2-positive classification in ESC.
Area of Science:
- Oncology
- Genetics
- Pathology
Background:
- Targeted anti-human epidermal growth factor receptor 2 (HER2) therapy is standard for advanced/recurrent HER2-positive endometrial serous carcinoma (ESC).
- A specific HER2 testing algorithm for ESC is proposed, but comprehensive studies on HER2 gene amplification features are lacking.
Purpose of the Study:
- To evaluate HER2 amplification characteristics in ESC using breast and gastric HER2 fluorescence in situ hybridization (FISH) guidelines.
Main Methods:
- Ninety-four ESCs with available HER2 immunohistochemistry (IHC) and FISH were analyzed.
- HER2 IHC was scored using a proposed ESC-specific algorithm.
- FISH was evaluated against 2018 ESC clinical trial criteria, ASCO/CAP 2016 gastric criteria, and ASCO/CAP 2013/2018 breast criteria.
Main Results:
- Most tumors (90.4%) had a 2+ HER2 IHC score.
- Polysomy of chromosome 17 was observed in 16% of tumors.
- HER2 FISH interpretation using clinical trial criteria showed 99% concordance with current gastric and breast HER2 FISH interpretations.
Conclusions:
- Clinical trial criteria for HER2 FISH in ESC are supported, with a proposed modification for HER2-positive classification.
- The modification includes HER2 IHC 2+, HER2/CEP17 ratio < 2.0, and average HER2 copy number ≥ 6.0.
- Further clinical studies are needed to correlate specific HER2 FISH categories with therapeutic response.
More Related Videos
10:21Protocol for HER2 FISH Using a Non-cross-linking, Formalin-free Tissue Fixative to Combine Advantages of Cryo-preservation and Formalin Fixation
Published on: December 25, 2017
11:34Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017