Related Experiment Video
Updated: Jun 17, 2025
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
Interobserver Variability in HER-2 Immunostaining Interpretation of Metastatic HER2 Low Breast Cancers in Cytology
Niyati Desai1, Courtney F Connelly1, Simon Sung2
1Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Background:
Approximately, 55% of breast carcinomas are reported to be HER-2 low breast carcinomas. Trastuzumab-Deruxtecan is a new FDA-approved targeted therapy for HER-2 low metastatic breast carcinomas, making it essential that all efforts are made to identify these tumors in specimens submitted for pathologic examination. Cytology specimens are often the first and only modality of this assessment due to the ease of specimen procurement. This study aimed to determine the variability in HER-2 immunostaining interpretation among observers using cytologic specimens from metastatic sites.
Design:
A pathology database search was made to identify metastatic breast carcinoma reported in cytology specimens. A manual search was then done to identify cases of HER-2 low category, H&E cell block and HER-2 neu immunostain slides were retrieved for a total of 50 cases. Reviewer #1 and #2 independently interpreted HER-2 immunostain of all 50 cases. Only discordant cases were sent for reviewer-3 interpretation. All three were blinded by the metastatic site, and original HER-2 interpretation.
Results:
Of 50 cases, 11 cases (22%) were reported as concordant scores between reviewer #1 and reviewer #2 but had a discordant original IHC report. Additionally, 4 cases (8%) had discordant reporting of HER2 IHC stain between reviewer #1 and reviewer #2 making a total of 15 cases (30%) with overall discordant results.
Conclusion:
This study highlights the interobserver variability of HER-2 immunostain interpretation for HER-2 low category of breast carcinomas. We recommend the need for more robust laboratory techniques including molecular for uniform identification of these unique targetable metastatic breast carcinoma groups.
Insights
Interobserver variability in HER2 immunostaining interpretation for HER2 low breast cancer was observed in 30% of cases. This highlights the need for improved laboratory techniques for accurate identification of these targetable metastatic breast carcinomas.
Area of Science:
- Oncology
- Pathology
- Immunohistochemistry
Background:
- Approximately 55% of breast carcinomas are HER2 low.
- Trastuzumab-Deruxtecan is a targeted therapy for HER2 low metastatic breast cancer.
- Cytology specimens are crucial for initial assessment due to ease of procurement.
Purpose of the Study:
- To determine the variability in HER2 immunostaining interpretation among observers.
- To assess HER2 interpretation in cytologic specimens from metastatic breast cancer sites.
Main Methods:
- Retrieved 50 metastatic breast carcinoma cases from a pathology database.
- Two independent reviewers interpreted HER2 immunostains on H&E cell blocks.
- Discordant cases were reviewed by a third reviewer, blinded to metastatic site and original interpretation.
Main Results:
- 11 cases (22%) showed concordance between reviewers but discordance with the original IHC report.
- 4 cases (8%) had discordant HER2 IHC stain reporting between the two reviewers.
- Overall, 30% of cases exhibited discordant results.
Conclusions:
- Significant interobserver variability exists in HER2 immunostain interpretation for HER2 low breast carcinomas.
- More robust laboratory techniques, including molecular methods, are recommended for uniform identification.
- Accurate identification is essential for targeted therapy selection in metastatic breast cancer.
