TY - JOUR
T1 - Microsatellite instability in prostate cancer by PCR or next-generation sequencing
AU - Hempelmann, Jennifer A.
AU - Lockwood, Christina M.
AU - Konnick, Eric Q.
AU - Schweizer, Michael T.
AU - Antonarakis, Emmanuel S.
AU - Lotan, Tamara L.
AU - Montgomery, Bruce
AU - Nelson, Peter S.
AU - Klemfuss, Nola
AU - Salipante, Stephen J.
AU - Pritchard, Colin C.
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/4/17
Y1 - 2018/4/17
N2 - 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.
AB - 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.
KW - Capillary electrophoresis
KW - MSI
KW - MSINGS
KW - Microsatellite instability
KW - Mismatch repair
KW - NGS
KW - Next-generation sequencing
KW - Promega
KW - Prostate adenocarcinoma
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U2 - 10.1186/s40425-018-0341-y
DO - 10.1186/s40425-018-0341-y
M3 - Article
C2 - 29665853
AN - SCOPUS:85045514517
SN - 2051-1426
VL - 6
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 1
M1 - 29
ER -