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Research Article
Hideyuki Hayashi
Keio University
Corresponding Author
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Background: Various malignancies exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The MSI-IVD kit, which can detect MSI status using a polymerase chain reaction (PCR)-based method, was approved as the first tumor-agnostic companion diagnostic for pembrolizumab in patients with MSI-H solid tumors in Japan. Recently, next-generation sequencing (NGS), which can also detect MSI-H/dMMR, has been made clinically available. However, the real-world concordance in MSI-H/dMMR between the PCR-based testing and NGS is yet to be thoroughly investigated.
Methods: A retrospective study was conducted to evaluate the utility of MSI testing using PCR-based testing and NGS assay in patients eligible for both MSI testing and any NGS platform. Co-primary endpoints included positive and negative predictive values of MSI-H/dMMR.
Results: Between December 2018 and June 2020, 40 patients underwent both PCR-based MSI testing and NGS assay for MSI. Two patients with gastric neuroendocrine carcinoma and ovarian cancer were confirmed to have MSI-H/dMMR in both examinations. Among the 38 patients diagnosed as microsatellite stable by PCR-based testing, 2 (5.2%) with pancreatic cancer were diagnosed as MSI-H after NGS analyses. NGS had positive and negative predictive values of 100% (2/2) and 94.7% (36/38), respectively, for MSI-H, while the concordance between NGS and PCR-based testing was 94.9% (38/40).
Conclusion: Similar to PCR-based MSI testing, NGS can be useful for evaluating MSI/MMR status in clinical practice and could be an important alternative method for detecting MSI-H/dMMR in the future.
Keywords
clinical cancer research, genome-wide sequencing, DNA repair, medical oncology
Figure 1
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No competing interests reported.
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A new preprint design is coming!
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Hideyuki Hayashi
Keio University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 28 May, 2021
No community comments so far
Editorial decision: Major revision
On 12 Jul, 2021
Reviews received
Received 08 Jul, 2021
Reviewers agreed
On 29 Jun, 2021
Reviewers agreed
On 21 Jun, 2021
Reviewers invited
Invitations sent on 21 Jun, 2021
Editor assigned
On 21 Jun, 2021
Editor invited
On 28 May, 2021
Submission checks complete
On 26 May, 2021
First submitted
On 24 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Various malignancies exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The MSI-IVD kit, which can detect MSI status using a polymerase chain reaction (PCR)-based method, was approved as the first tumor-agnostic companion diagnostic for pembrolizumab in patients with MSI-H solid tumors in Japan. Recently, next-generation sequencing (NGS), which can also detect MSI-H/dMMR, has been made clinically available. However, the real-world concordance in MSI-H/dMMR between the PCR-based testing and NGS is yet to be thoroughly investigated.
Methods: A retrospective study was conducted to evaluate the utility of MSI testing using PCR-based testing and NGS assay in patients eligible for both MSI testing and any NGS platform. Co-primary endpoints included positive and negative predictive values of MSI-H/dMMR.
Results: Between December 2018 and June 2020, 40 patients underwent both PCR-based MSI testing and NGS assay for MSI. Two patients with gastric neuroendocrine carcinoma and ovarian cancer were confirmed to have MSI-H/dMMR in both examinations. Among the 38 patients diagnosed as microsatellite stable by PCR-based testing, 2 (5.2%) with pancreatic cancer were diagnosed as MSI-H after NGS analyses. NGS had positive and negative predictive values of 100% (2/2) and 94.7% (36/38), respectively, for MSI-H, while the concordance between NGS and PCR-based testing was 94.9% (38/40).
Conclusion: Similar to PCR-based MSI testing, NGS can be useful for evaluating MSI/MMR status in clinical practice and could be an important alternative method for detecting MSI-H/dMMR in the future.
Figure 1
Figure 2
No competing interests reported.
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