Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Comprehensive Study of Microsatellite Instability Testing and Its Comparison With Immunohistochemistry in Gastric Cancers

  • Yujun Park (Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Soo Kyung Nam (Department of Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine) ;
  • Soo Hyun Seo (Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Kyoung Un Park (Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Hyeon Jeong Oh (Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Young Suk Park (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Yun-Suhk Suh (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Sang-Hoon Ahn (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Do Joong Park (Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Hyung-Ho Kim (Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine) ;
  • Hye Seung Lee (Cancer Research Institute, Seoul National University)
  • Received : 2022.10.04
  • Accepted : 2022.12.23
  • Published : 2023.04.30
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Abstract

Purpose: In this study, polymerase chain reaction (PCR)-based microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for mismatch repair (MMR) protein expression in patients with gastric cancer (GC). Materials and Methods: In 5,676 GC cases, PCR-based MSI testing using five microsatellites (BAT-26, BAT-25, D5S346, D2S123, and D17S250) and IHC for MLH1 were performed. Reevaluation of MSI testing/MLH1 IHC and additional IHC for MSH2, MSH6, and PMS2 were performed in discordant/indeterminate cases. Results: Of the 5,676 cases, microsatellite stable (MSS)/MSI-low and intact MLH1 were observed in 5,082 cases (89.5%), whereas MSI-high (MSI-H) and loss of MLH1 expression were observed in 502 cases (8.8%). We re-evaluated the remaining 92 cases (1.6%) with a discordant/indeterminate status. Re-evaluation showed 1) 37 concordant cases (0.7%) (18 and 19 cases of MSI-H/MMR-deficient (dMMR) and MSS/MMR-proficient (pMMR), respectively), 2) 6 discordant cases (0.1%) (3 cases each of MSI-H/pMMR and MSS/dMMR), 3) 14 MSI indeterminate cases (0.2%) (1 case of dMMR and 13 cases of pMMR), and 4) 35 IHC indeterminate cases (0.6%) (22 and 13 cases of MSI-H and MSS, respectively). Finally, MSI-H or dMMR was observed in 549 cases (9.7%), of which 47 (0.8%) were additionally confirmed as MSI-H or dMMR by reevaluation. Sensitivity was 99.3% for MSI testing and 95.4% for MMR IHC. Conclusions: Considering the low incidence of MSI-H or dMMR, discordant/indeterminate results were occasionally identified in GCs, in which case complementary testing is required. These findings could help improve the accuracy of MSI/MMR testing in daily practice.

Keywords

Acknowledgement

This work was supported by the Technology development Program (S2638360) funded by the Ministry of SMEs and Startups (MSS, Korea).

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