Abstract
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.
29 Comprehensive molecular assessment of mismatch repair deficiency in lynch-associated ovarian cancers using next-generation sequencing (NGS) panel
