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Validation of Linear Range HER2/Estrogen Receptor/Progesterone Receptor IHControls for Daily Quality Assurance
Seshi R Sompuram1, Kodela Vani1, Lori Ryan2
1Boston Cell Standards, Boston MA, USA.
Insights
The new FDA-cleared IHControls demonstrate high concordance with traditional tissue controls for HER2, ER, and PR testing. These controls accurately detect immunohistochemistry (IHC) assay issues, offering reliable performance in clinical settings.
Area of Science:
- Biomedical diagnostics
- Immunohistochemistry
- Quality control
Background:
- Immunohistochemistry (IHC) is crucial for cancer diagnostics, relying on accurate controls.
- Traditional tissue controls can have variability and limitations.
- A new FDA-cleared control, IHControls, utilizes peptide epitopes on microspheres.
Purpose of the Study:
- To evaluate the performance of IHControls for HER2, estrogen receptor (ER), and progesterone receptor (PR).
- To compare IHControls against conventional tissue controls in clinical IHC laboratories.
- To assess the sensitivity, reproducibility, and specificity of IHControls.
Main Methods:
- Side-by-side comparison of IHControls and tissue/cell line controls across 5 clinical labs.
- Simulated IHC assay failure experiments using primary antibody dilution.
- Evaluation of lot-to-lot manufacturing reproducibility and specificity against irrelevant stains.
Main Results:
- Achieved 99.6% concordance between IHControls and tissue controls across 766 evaluations.
- Both control types demonstrated similar sensitivity in detecting IHC assay errors.
- IHControls showed <10% variability in manufacturing reproducibility and no cross-reactivity.
Conclusions:
- IHControls are the first FDA-cleared IHC controls.
- They offer sensitive and accurate detection of IHC assay problems.
- Performance is comparable to traditional tissue controls.
Objectives:
To evaluate a new US Food and Drug Administration (FDA)-cleared immunohistochemistry (IHC) control (IHControls [Boston Cell Standards]) comprising peptide epitopes for HER2, estrogen receptor (ER), and progesterone receptor (PR) attached to cell-sized microspheres and to compare its performance against conventional tissue controls.
Methods:
IHControls and tissue/cell line controls for HER2, ER, and PR were compared side by side daily at 5 clinical IHC laboratories for 1 to 2 months. Separately, the sensitivity of the 2 types of controls was evaluated in simulated IHC assay failure experiments by diluting the primary antibody. Additional evaluations included lot-to-lot manufacturing reproducibility of 3 independent lots and specificity against 26 antigenically irrelevant IHC stains.
Results:
Side-by-side testing revealed a 99.6% concordance between IHControls and tissue controls across 5 IHC laboratories and 766 individual evaluations. Three discordant quality control events were the result of operator error. Simulated assay failure data showed that both IHControls and tissue controls are similarly capable of detecting IHC staining errors. Manufacturing reproducibility of IHControls showed less than 10% variability (coefficient of variation). No cross-reactions were detected from 26 antigenically irrelevant IHC stains.
Conclusions:
IHControls, the first FDA-cleared IHC controls, can sensitively and accurately detect IHC assay problems, similar to tissue controls.
