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Microsatellite instability analysis: a multicenter study for reliability and quality control

T Bocker1, J Diermann, W Friedl

  • 1Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. T_Bocker@lac.jci.tju.edu

Cancer Research
|November 14, 1997
PubMed
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This study evaluated microsatellite instability (MSI) analysis reliability across eight labs for colorectal cancer. While identifying stable and unstable tumors was consistent, interpreting marker patterns varied, highlighting the need for standardized MSI reporting criteria.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Microsatellite instability (MSI) analysis is crucial for diagnosing hereditary non-polyposis colorectal cancer.
  • Multicenter studies are essential for assessing the reliability and quality of diagnostic techniques.

Purpose of the Study:

  • To evaluate the reliability and quality of microsatellite instability (MSI) analysis in diagnosing colorectal carcinomas.
  • To compare MSI analysis results from eight different laboratories using matched normal and tumor DNA samples.

Main Methods:

  • Eight laboratories performed MSI analysis on 10 matched pairs of normal and tumor DNA from colorectal carcinoma patients.
  • Various techniques were employed, including polyacrylamide gel electrophoresis with silver/ethidium bromide staining, radioactive labeling, and automated fluorescence detection.

Related Experiment Videos

  • A panel of over 30 primers per case was analyzed to assess microsatellite changes.

    • Main Results:

    • High concordance was observed in identifying highly unstable tumors and tumors without MSI.
    • Divergent classifications occurred in a significant fraction of cases due to varied interpretation of band patterns at several microsatellite marker loci.
    • Analysis of over 30 primers per case indicated that expanding the microsatellite panel beyond 10 loci did not significantly alter results.

    Conclusions:

    • Standardized criteria for MSI analysis, including a proposed panel of five microsatellite loci, are needed to improve inter-study comparability.
    • A tiered approach, expanding the panel if initial results are inconclusive, is suggested.
    • Reporting the number of loci analyzed and the number of unstable loci is recommended for consistent MSI reporting.