Association of MLH1, MSH2, MSH6, and PMS2 Protein Expression Levels with Clinicopathological Features in Colorectal Cancer Tissues

Overview

This study evaluates the prevalence of deficient mismatch repair (dMMR) in colorectal cancer (CRC) patients and its association with various clinicopathological features. Findings indicate that dMMR CRCs are more likely to be located in the right colon, poorly differentiated, and larger in size, with a lower likelihood of lymph node metastasis.

Background

Colorectal cancer (CRC) is a prevalent malignancy with significant mortality rates globally. The presence of dMMR is associated with distinct clinical features and has implications for treatment decisions, particularly regarding immunotherapy. Understanding the clinicopathological characteristics of dMMR CRC can aid in the management and screening of patients.

Data Highlights

Key Findings

• 22.5% of patients exhibited dMMR status.
• Isolated PMS2 loss was the most common deficiency pattern (50% of dMMR cases).
• dMMR CRCs were significantly more likely to be located in the right colon (61.1% vs. 22.6%, P < 0.001).
• Patients with dMMR CRC were more likely to have poorly differentiated tumors (50.0% vs. 19.4%, P = 0.009).
• dMMR status was associated with a lower rate of lymph node metastasis (22.2% vs. 46.8%, P = 0.052).
• Forward stepwise multivariable analysis identified right colon location, poor differentiation, and mucinous histology as independent predictors of dMMR.

Clinical Implications

Routine immunohistochemistry (IHC) testing for MMR proteins is recommended for CRC patients to identify dMMR status. Understanding the clinicopathological features associated with dMMR can guide treatment decisions, particularly regarding the use of immunotherapy and further genetic testing for Lynch syndrome.

Conclusion

The study highlights the prevalence and distinct clinicopathological profile of dMMR CRCs, emphasizing the importance of MMR testing in clinical practice. Further confirmatory testing is essential for accurate diagnosis and treatment planning.

Related Resources & Content

1. Evaluation of Clinical Features Associated with Mismatch Repair Deficiency in Colorectal Cancer: A Retrospective Multicenter Study, 2024 -- https://link.springer.com/article/10.1007/s00384-024-04674-z
2. Analysis and Comparison of Immune Profiles at the Tumor Invasion Front in pMMR/MSI-H and pMMR/MSS Colorectal Cancer Patients, 2025 -- https://link.springer.com/article/10.1007/s00384-025-05033-2
3. Prognostic Implications of Microsatellite Instability in Colorectal Cancer: Findings from a Multi-Center Study in Sweden, 2023 -- https://link.springer.com/article/10.1007/s00384-023-04480-z
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5. Mismatch Repair and Microsatellite… | College of American Pathologists -- https://www.cap.org/protocols-and-guidelines/cap-guidelines/current-cap-guidelines/mismatch-repair-and-microsatellite-instability-testing-for-immune-checkpoint-inhibitor-therapy?utm_source=openai
6. Evaluation of Clinical Features Associated with Mismatch Repair Deficiency in Colorectal Cancer: A Retrospective Multicenter Study
7. Analysis and Comparison of Immune Profiles at the Tumor Invasion Front in pMMR/MSI-H and pMMR/MSS Colorectal Cancer Patients
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