Microsatellite Instability in Prostate Cancer by PCR or Next-Generation Sequencing.

BACKGROUND: Microsatellite instability (MSI) is now being used as a sole biomarker to guide immunotherapy treatment for men with advanced prostate cancer. Yet current molecular diagnostic tests for MSI have not been evaluated for use in prostate cancer.

METHODS: We evaluated two next-generation sequencing (NGS) MSI-detection methods, MSIplus (18 markers) and MSI by Large Panel NGS (> 60 markers), and compared the performance of each NGS method to the most widely used 5-marker MSI-PCR detection system.   All methods were evaluated by comparison to targeted whole gene sequencing of DNA mismatch-repair genes, and immunohistochemistry for mismatch repair genes, where available.

RESULTS: In a set of 91 prostate tumors with known mismatch repair status (29-deficient and 62-intact mismatch-repair) MSIplus had a sensitivity of 96.6% (28/29) and a specificity of 100% (62/62), MSI by Large Panel NGS had a sensitivity of 93.1% (27/29) and a specificity of 98.4% (61/62), and MSI-PCR had a sensitivity of 72.4% (21/29) and a specificity of 100% (62/62).

CONCLUSIONS: We found that the widely used 5-marker MSI-PCR panel has inferior sensitivity when applied to prostate cancer and that NGS testing with an expanded panel of markers performs well. In addition, NGS methods offer advantages over MSI-PCR, including no requirement for matched non-tumor tissue and an automated analysis pipeline with quantitative interpretation of MSI-status.

J Immunother Cancer. 2018 Apr 17 [Epub]

Jennifer A. Hempelmann, Christina M. Lockwood, Eric Q. Konnick, Michael T. Schweizer, Emmanuel S. Antonarakis, Tamara L. Lotan, Bruce Montgomery, Peter S. Nelson, Nola Klemfuss, Stephen J. Salipante and Colin C. Pritchard

1. Department of Laboratory Medicine, University of Washington, Seattle, Washington
2. Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, Washington
3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
4. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland
5. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
6. VA Puget Sound Health Care System, Seattle, Washington
7. Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
8. Department of Laboratory Medicine, University of Washington, Seattle, Washington

J Immunother Cancer. 2018 Apr 17;6(1):29. doi: 10.1186/s40425-018-0341-y.
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