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Background <p>High microsatellite instability (MSI-H) is an established prognostic marker in various cancers, including colorectal, gastric, and endometrial cancers. However, comprehensive real-world data from universal screening in Asian populations remain limited. We aimed to evaluate the clinicopathological and prognostic impact of MSI-H status in Japanese patients with colorectal cancer (CRC).</p> Methods <p>This retrospective cohort study was conducted at Osaka General Medical Center, Japan. A total of 346 consecutive patients with CRC who underwent MSI testing between January 2021 and December 2022 were retrospectively analyzed. MSI status and associated clinicopathological features were assessed. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier survival curves and Cox regression models.</p> Results <p>Among the 346 patients, 29 (8.4%) had MSI-H tumors, which were more frequently right-sided (<i>p</i> &lt;0.0001) and poorly differentiated (<i>p</i> &lt;0.0001) compared with non-MSI-H. Genomic analysis revealed that MSI-H tumors had significantly fewer <i>RAS</i> mutations (<i>p</i> = 0.024) and more <i>BRAF</i> mutations (<i>p</i> &lt;0.0001) compared with non-MSI-H tumors. Survival analysis showed no significant differences in RFS (HR, 0.67; 95% CI, 0.26–1.90; <i>p</i> = 0.40) or OS (HR, 0.64; 95% CI, 0.30–1.58; <i>p</i> = 0.78) between patients with MSI-H and non–MSI-H tumors. Multivariate analysis identified MSI-H as a potential independent predictor of favorable OS (HR, 0.07; 95% CI, 0.005–0.90; <i>p</i> = 0.04), whereas <i>BRAF</i> mutations were associated with poor OS (HR, 7.39; 95% CI, 1.32–41.50; <i>p</i> = 0.02).</p> Conclusions <p>This real-world study suggests that MSI-H status is associated with distinct clinicopathological characteristics and may be associated with improved overall survival in Japanese patients with CRC undergoing universal MSI screening. These findings support the clinical relevance of MSI testing in routine clinical practice and highlight the need for further validation in a larger cohort.</p>

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Clinicopathological characteristics and prognostic outcomes in consecutive Japanese patients with high microsatellite-instability colorectal cancer: real-world data from universal screening

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  • 发表日期：

    2026年3月13日

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  • Akira Inoue,
  • Yujiro Nishizawa,
  • Masahiro Hashimoto,
  • Yuki Ozato,
  • Yoshihiro Morimoto,
  • Kenta Furukawa,
  • Masashi Hirota,
  • Yasuhiro Miyazaki,
  • Akira Tomokuni,
  • Masaaki Motoori,
  • Kazumasa Fujitani

摘要

Background

High microsatellite instability (MSI-H) is an established prognostic marker in various cancers, including colorectal, gastric, and endometrial cancers. However, comprehensive real-world data from universal screening in Asian populations remain limited. We aimed to evaluate the clinicopathological and prognostic impact of MSI-H status in Japanese patients with colorectal cancer (CRC).

Methods

This retrospective cohort study was conducted at Osaka General Medical Center, Japan. A total of 346 consecutive patients with CRC who underwent MSI testing between January 2021 and December 2022 were retrospectively analyzed. MSI status and associated clinicopathological features were assessed. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan–Meier survival curves and Cox regression models.

Results

Among the 346 patients, 29 (8.4%) had MSI-H tumors, which were more frequently right-sided (p <0.0001) and poorly differentiated (p <0.0001) compared with non-MSI-H. Genomic analysis revealed that MSI-H tumors had significantly fewer RAS mutations (p = 0.024) and more BRAF mutations (p <0.0001) compared with non-MSI-H tumors. Survival analysis showed no significant differences in RFS (HR, 0.67; 95% CI, 0.26–1.90; p = 0.40) or OS (HR, 0.64; 95% CI, 0.30–1.58; p = 0.78) between patients with MSI-H and non–MSI-H tumors. Multivariate analysis identified MSI-H as a potential independent predictor of favorable OS (HR, 0.07; 95% CI, 0.005–0.90; p = 0.04), whereas BRAF mutations were associated with poor OS (HR, 7.39; 95% CI, 1.32–41.50; p = 0.02).

Conclusions

This real-world study suggests that MSI-H status is associated with distinct clinicopathological characteristics and may be associated with improved overall survival in Japanese patients with CRC undergoing universal MSI screening. These findings support the clinical relevance of MSI testing in routine clinical practice and highlight the need for further validation in a larger cohort.