Abstract 108P
Background
The human epidermal growth factor receptor 2 (HER2/neu) play a predictive and prognostic role in colorectal cancer (CRC). Accurate evaluating of HER2 overexpression is required for selection and determination of eligible patients for HER2-directed therapy or primary resistance and poor response to anti-EGFR therapy. However, there is no currently established best practice for HER2 testing and interpretation in CRC. The purpose of this study was to validate and evaluate the performance of AmoyDx® HANDLE Classic NGS Panel (CP40) in assessing HER2 status by comparing it with HER2 IHC (4B5)/FISH analysis.
Methods
The CP40 is based on Halo-shape ANnealing and Defer-Ligation Enrichment (HANDLE) system technology, which allows high sensitivity in 40 key solid tumour genes qualitative detection and microsatellite instability (MSI) status assessment utilizing DNA and RNA. Performance of the CP40 was compared against the HER2 IHC/FISH assay according to the HERACLES scoring criteria using 805 CRC samples. Only samples with a ratio ERBB2:CEN17 ≥ 2 or staining equivocal (2+) or positive (3+) in at least 50% of cells were determined as HER2 IHC/FISH positive.
Results
CP40 and IHC/FISH assays were highly concordant in their assessment of HER2 status in CRCs (99.50%, 801/805, kappa = 0.892). Three conflicting results were negative in CP40 but were scored 2+ in 50-70% of the cells and identified as positive by IHC/FISH. One CRC scored as 3+ in 40% cells was determined to be negative by both CP40 and IHC/FISH. And all MSI CRCs were evaluated as HER2 negative by both CP40 and IHC. Table: 108P
Comparison of HER2 status determined from CP40 and IHC/FISH assays
| ERBB2 NGS-based CNV testing | ||||
| True | False | Total | ||
| HER2 IHC/FISH assay | Positive | 17 | 3 | 20 |
| Negative | 1 | 784 | 785 | |
| Total | 18 | 787 | 805 | |
| Kappa= | 0.892 | |||
| Overall coincidence rate = | 99.50% |
Conclusions
CRC-specific HER2 testing protocols and HER2 scoring criteria still needs to be optimised in a more refined and defined manner. HANDLE-based CP40, which combines DNA and RNA in NGS testing, is a potent tool for sensitive and reliable detection of HER2 status in clinical diagnostics.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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