[Microsatellite instability : Review of methods and applications]

Area of Science:

• Oncology
• Molecular Pathology
• Cancer Genetics

Background:

• Microsatellite instability (MSI) and loss of mismatch repair proteins (MMRD) were initially identified as markers for Lynch syndrome (LS), a hereditary cancer predisposition syndrome.
• The clinical utility of MSI/MMRD testing has expanded significantly, now serving as a critical biomarker for predicting patient response to checkpoint immunotherapies.

Purpose of the Study:

• To review the current applications and methodologies of MSI/MMRD testing in tumor pathology.
• To highlight the evolving role of MSI/MMRD as a predictive biomarker for immunotherapy response in advanced cancers.

Main Methods:

• Microsatellite instability (MSI) detection using polymerase chain reaction (PCR)-based technologies.
• Assessment of mismatch repair protein (MMRD) loss.
• Utilizing next-generation sequencing (NGS) methods for MSI analysis.
• Application of these tests across various tumor entities, with a focus on colorectal, endometrial, and gastric cancers.

Main Results:

• MSI/MMRD testing is established as a predictive biomarker for therapy response to checkpoint immunotherapies in advanced carcinomas.
• The diagnostic approach for MSI/MMRD varies depending on specific tumor types and the chosen testing methodology (PCR vs. NGS).

Conclusions:

• MSI/MMRD testing is an indispensable tool in modern tumor pathology, with broad indications.
• Its role extends from cancer predisposition screening (Lynch syndrome) to guiding therapeutic decisions, particularly in immunotherapy for advanced cancers like colorectal, endometrial, and gastric malignancies.