Microsatellite instability in prostate cancer by PCR or next-generation sequencing. Issue 1 (17th April 2018)

• Record Type: Journal Article
• Authors: Hempelmann, Jennifer A.; Lockwood, Christina M.; Konnick, Eric Q.; Schweizer, Michael T.; Antonarakis, Emmanuel S.; Lotan, Tamara L.; Montgomery, Bruce; Nelson, Peter S.; Klemfuss, Nola; Salipante, Stephen J.; Pritchard, Colin C.
• Is Part Of: Journal for immunotherapy of cancer. Volume 6:Issue 1(2018)
• Publication Date: 2018-04-17
• Subjects: Prostate adenocarcinoma -- Microsatellite instability -- MSI -- Promega -- Capillary electrophoresis -- Mismatch repair -- NGS -- Next-generation sequencing -- mSINGS; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-018-0341-y
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : 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.