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Microsatellite instability in prostate cancer by PCR or next-generation sequencing
Jennifer A Hempelmann1, Christina M Lockwood1, Eric Q Konnick1
1Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Next-generation sequencing (NGS) methods for microsatellite instability (MSI) detection show superior sensitivity and specificity in prostate cancer compared to traditional MSI-PCR tests. These advanced NGS approaches are better suited for guiding immunotherapy in advanced prostate cancer patients.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Microsatellite instability (MSI) is a key biomarker for immunotherapy selection in advanced prostate cancer.
- Current diagnostic tests for MSI lack validation in prostate cancer specimens.
Purpose of the Study:
- To evaluate the performance of two next-generation sequencing (NGS) based MSI detection methods.
- To compare NGS methods against the standard 5-marker MSI-PCR test for prostate cancer.
Main Methods:
- Two NGS panels (MSIplus with 18 markers, Large Panel NGS with >60 markers) were assessed.
- Performance was benchmarked against a 5-marker MSI-PCR assay.
- Validation involved comparison with targeted gene sequencing and immunohistochemistry for DNA mismatch-repair genes.
Main Results:
- MSIplus achieved 96.6% sensitivity and 100% specificity.
- Large Panel NGS demonstrated 93.1% sensitivity and 98.4% specificity.
- The 5-marker MSI-PCR assay showed lower sensitivity (72.4%) but 100% specificity.
Conclusions:
- The 5-marker MSI-PCR panel exhibits inadequate sensitivity for prostate cancer.
- NGS methods, particularly with larger marker panels, offer robust and reliable MSI detection in prostate cancer.
- NGS provides advantages including no need for non-tumor tissue and automated, quantitative analysis.
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