Are High Levels of Microsatellite Instability and Microsatellite Stability Identical in DNA Mismatch Repair-Deficient Colorectal Cancer Patients?

Abstract

Purpose. The purpose of the current study was to determine whether there is a difference between high levels of microsatellite instability (MSI-H) and microsatellite stability (MSS) in DNA mismatch repair-deficient (DMMR) colorectal cancer (CRC) patients. Methods. A total of 452 CRC patients with DMMR from December, 2014, to April, 2021, in our hospital were selected retrospectively. However, only 105 patients underwent Sanger or next-generation-sequencing (NGS) to confirm their microsatellite status. Ultimately, 55 MSI-H patients and 20 MSS patients with intact medical record information were included in this study. Results. The MSS group was associated with a higher mutation rate in the KRAS gene ( P = 0.011 ). Meanwhile, MSI-H was related to colon cancer ( P < 0.01 ). However, no significant differences in other clinical characteristics were observed between the two groups of patients. There was no significant difference between the MSI-H and MSS groups in terms of overall survival (OS) ( P = 0.398 ) and disease-free survival (DFS) ( P = 0.307 ). Conclusion. The MSI-H status was associated with colon cancer and a lower mutation rate of the KRAS gene in DMMR patients. In CRC-DMMR patients, the MSS group exhibited better OS and DFS than the MSI-H group, although these differences were not statistically significant. Accordingly, in clinical practice, we should not confuse these two types of patients.

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

“…dMMR, on the other hand, results from the loss of function in the DNA mismatch repair system, a crucial mechanism responsible for correcting errors in DNA replication. 36 Both MSI and dMMR can significantly influence the prognosis and therapeutic strategies for colorectal cancer patients. The DNA mismatch repair system comprises a set of proteins responsible for detecting and repairing errors that occur during DNA replication.…”

“…MSI is characterized by a high frequency of mutations in microsatellites, short repetitive DNA sequences scattered throughout the genome. dMMR, on the other hand, results from the loss of function in the DNA mismatch repair system, a crucial mechanism responsible for correcting errors in DNA replication . Both MSI and dMMR can significantly influence the prognosis and therapeutic strategies for colorectal cancer patients.…”