TEST:

VENTANA HER2 Dual ISH DNA Probe Cocktail

In this study, 3 pre-analytical components were assessed for the VENTANA Kappa and Lambda Dual ISH mRNA Probe Cocktail Assay. There are many acceptable tissue thickness, fixation, and decalcification options that are compatible with this assay.

We demonstrate HER2 protein overexpression and gene amplification in 20% and 66% of SMARCA4-d GECs, respectively. Our results suggest anti-HER2 therapy may be considered as an alternative therapeutic avenue in these aggressive carcinomas. Importantly, overexpression and amplification are not always concordant, bringing into question the utility of current HER2-testing guidelines in this context.SMARCA4-Deficient Gastroesophageal Carcinoma Findings

A significant limitation was the high number of invalid plasma tests due to pre-analytical handling errors or transport issues. Nonetheless, plasma testing (liquid biopsy) proved useful for monitoring tumor evolution and assessing residual disease.

In this large study using optimized UC-specific assays, 56% of UC samples were HER2+ or HER2-low. HER2 gene amplification was present in a subset of samples across HER2 expression levels by IHC. Accurate analysis of HER2 expression in UC could enable a clinically meaningful impact on this disease through the development of HER2-targeted therapies.

Background: HER2 gene amplification, poor prognostic factor in IBC, has emerged as valuable predictive marker for improved patient survival with anti-HER2 therapies like Trastuzumab... The uPath IA algorithm tool by Roche Diagnostics was validated with significant concordance and sensitivity. It is non-inferior to manual assessment with capability to improve workflow efficiency.

By in-house DISH, highly equivocal cases can be discussed in a multidisciplinary manner to make the best decision for patients. Reduced TAT enables 200% faster initiation of systemic therapies to those in need. Sheffield is a consultant for, and has received research support from, Amgen, Astra Zeneca, Bayer, Biocartis, Boehringer-Ingelheim, Cell Marque, Elevation Oncology, Eli Lily, EMD Serono, Incyte, Janssen, Merck, Novartis, Pfizer, Roche, Thermo Fisher, and Turning Point Therapeutics.

Unlike HER2 positivity, there is no gold standard or reflex test to confirm HER2-low expression. Before conducting clinical trials or applying the new ADCs, each pathology laboratory should verify IHC conditions to accurately identify HER2-low breast cancer.

Detection of HER2 amplification in plasma was accurate, as indicated by the low rate of false positives; however, sensitivity was poor. This suggests that ctDNA testing may help identify pts with HER2 amplification but is not yet a substitute for tissue-based HER2 ISH and IHC testing.

"We successfully validated the latest version of D-DISH assay as a substitute for FISH in predicting HER2 gene status with significant interobserver reproducibility, concluding that this D-DISH assay may be introduced in routine diagnostic services as a reflex test to ascertain HER2 gene status."

The SLR revealed wide variability of HER2 status in LA/mUC, highlighting a lack of standardized methods for assessing and defining HER2 status. In our large study using standardized laboratory methods, 44% of UC samples were HER2+ or HER2-low, and HER2 status distribution was consistent with that reported for pts with LA/mUC. Results suggest a potentially important role for HER2-targeted therapy for UC.

Moreover, consistent benefit of T-DXd vs TPC was generally seen across patient groups with various tumor sample characteristics in DESTINY- Breast04. Determination of HER2-low status using the Ventana PATHWAY 4B5 IHC assay (and ISH when applicable) demonstrated the ability of the test, analyzed by pathologists using current ASCO/CAP guidelines, to identify pts who benefit from T-DXd.

Further, inter- and intra-reader agreement rates in the IA method were observed with point estimates of at least 96.7%. Overall, our data show that the uPath HER2 DISH IA is non-inferior to manual scoring and supports its use as an aid for pathologists in routine diagnosis of breast cancer.

Our study successfully validated the D-DISH test using the updated version of HER2 Dual ISH DNA Probe Cocktail Assay (Ventana Medical Systems, Inc., Tucson, AZ) as a substitute for FISH assay in accurately predicting the HER2 gene status with significant interobserver reproducibility. We conclude that this D-DISH test may be introduced in rouine diagnostic services as a reflex test for detecting HER2 gene status.

Comparison of agreement rates showed that the lower bounds of the difference of PPA and NPA 95% CIs were -0.9% and - 6.2%, respectively, and met the study’s pre-specified acceptance criteria. Overall, the validation studies demonstrated that the uPath HER2 Dual ISH Image Analysis method is equivalent to the manual scoring method in determining HER2 gene status in breast cancer.