Prognostic significance of microsatellite instability in colon cancer: Insights from a Propensity Score-Matched Study

•Despite previous research suggesting microsatellite instability (MSI) status as a significant prognostic factor in colon cancer, this study found that MSI status alone did not independently predict overall survival (OS) or disease-free survival (DFS) in colon cancer patients.•The study emphasized the multifactorial nature of colon cancer biology, suggesting that the influence of MSI status on prognosis may vary based on interactions with other molecular and clinicopathological factors, necessitating comprehensive prognostic assessment approaches.•Tumor staging, particularly stage N and stage M emerged as critical, independent prognostic factors for OS, underscoring the importance of comprehensive tumor staging in predicting patient outcomes and guiding treatment decisions.•Besides MSI status, factors such as tumor diameter and perineural invasion were identified as significant prognostic indicators. Larger tumor diameter and the presence of perineural invasion were associated with poorer outcomes, highlighting their roles in tumor aggressiveness and invasiveness.•While MSI status did not independently predict outcomes, understanding other prognostic factors, such as tumor staging and clinicopathological features, remains crucial for treatment decision-making and personalized medicine in colon cancer management.