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[Microsatellite instability : Review of methods and applications].

W Dietmaier1, R Büttner2, J Rüschoff3

  • 1Institut für Pathologie, Universität Regensburg, Regensburg, Deutschland.

Der Pathologe
|May 24, 2019
PubMed
Summary

Microsatellite instability (MSI) and loss of mismatch repair proteins (MMRD) are key biomarkers for Lynch syndrome and predicting immunotherapy response. These tests, using PCR or NGS, are vital in diagnosing and treating various cancers, including colorectal and gastric.

Keywords:
DNA mismatch repairGenetic predispositionNeoplasmsPredictive value of testsPrognosis

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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.