Search

* Context.--The authors announce the launch of the Consortium for Analytic Standardization in Immunohistochemistry, funded with a grant from the National Cancer Institute. As with other laboratory testing, analytic standards are important for many different stakeholders: commercial vendors of instruments and reagents, biopharmaceutical firms, pathologists, scientists, clinical laboratories, external quality assurance organizations, and regulatory bodies. Analytic standards are customarily central to assay development, validation, and method transfer into routine assays and are critical quality assurance tools. Objective.--To improve immunohistochemistry (IHC) test accuracy and reproducibility by integrating analytic standards into routine practice. To accomplish this mission, the consortium has 2 mandates: (1) to experimentally determine analytic sensitivity thresholds (lower and upper limits of detection) for selected IHC assays, and (2) to inform IHC stakeholders of what analytic standards are, why they are important, and how and for what purpose they are used. The consortium will then publish the data and offer analytic sensitivity recommendations where appropriate. These mandates will be conducted in collaboration and coordination with clinical laboratories, external quality assurance programs, and pathology organizations. Data Sources.--Literature review and published external quality assurance data. Conclusions.--Integration of analytic standards is expected to (1) harmonize and standardize IHC assays; (2) improve IHC test accuracy and reproducibility, both within and between laboratories; and (3) dramatically simplify and improve methodology transfer for new IHC protocols from published literature or clinical trials to clinical IHC laboratories. doi: 10.5858/arpa.2022-0031-RA, The new Consortium for Analytic Standardization in Immunohistochemistry (CASI) has been launched to build foundational evidence for integration of analytic standards into the routine practice of clinical and clinical research [...]

Aims: Recently, human epidermal growth factor 2 (HER2)‐low (i.e. HER2 score 1+ or 2+ without amplification) breast cancer patients became eligible for trastuzumab–deruxtecan treatment. To improve assay standardisation and detection of HER2‐low in a quantitative manner, we conducted an external quality assessment‐like study in the Netherlands. Dynamic range cell lines and immunohistochemistry (IHC) calibrators were used to quantify HER2 expression and to assess interlaboratory variability. Methods and results: Three blank slides with a dynamic range cell line and an IHC calibrator were stained with routine HER2 assays by 35 laboratories. Four different antibody clones were used: 19 (54.3%) 4B5, six (17.1%) A0485, five (14.3%) DG44 (HercepTest) and five (14.3%) SP3. Laboratories used two different detection kits for 4B5 assays: 14 (73.7%) ultraView and five (26.3%) OptiView. Variability of HER2 expression in cell lines, measured with artificial intelligence software, was median (min–max) = negative core 0.5% (0.0–57.0), 1+ core 4.3% (1.6–71.3), 2+ core 42.8% (30.4–92.6) and 3+ core 96.2% (91.8–98.8). The calibrators DG44 and 4B5 OptiView had the highest analytical sensitivity, closely followed by 4B5 ultraView. SP3 was the least sensitive. Calibrators of A0485 assays were not analysable due to background staining. Conclusions: As assays were validated for detecting HER2‐amplified tumours, not all assays and antibodies proved suitable for HER2‐low detection. Some tests showed distinct expression in the negative cell line. Dynamic range cell line controls and quantitative analysis using calibrators demonstrated more interlaboratory variability than commonly appreciated. Revalidation of HER2 tests by laboratories is needed to ensure clinical applicable HER2‐low assays. [ABSTRACT FROM AUTHOR]

To the Editor.--We, the undersigned, endorse the proposal published by Barbarajean Magnani, MD, PhD, and Clive Taylor, MD, Dphil, (1) in their recent Archives of Pathology & Laboratory Medicine editorial. [...]