Multi-center real-world comparison of the fully automated Idylla™ microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer

Virchows Arch. 2021 May;478(5):851-863. doi: 10.1007/s00428-020-02962-x. Epub 2020 Nov 10.

Abstract

Microsatellite instability (MSI) is present in 15-20% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla™ MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla™ testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla™ results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla™ MSI Assay were equally distributed over the seven biomarkers, and 84.48% of the MSI-high samples had ≥ 5 mutated biomarkers, while 98.25% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla™ MSI Assay and immunohistochemistry was 96.39% (988/1025); 17/37 discordant samples were found to be concordant when a third method was used. Compared with routine molecular methods, the concordance level was 98.01% (789/805); third-method analysis found concordance for 8/16 discordant samples. The failure rate of the Idylla™ MSI Assay (0.23%; 3/1301) was lower than that of referenced immunohistochemistry (4.37%; 47/1075) or molecular assays (0.86%; 7/812). In conclusion, lower failure rates and high concordance levels were found between the Idylla™ MSI Assay and routine tests.

Keywords: Colorectal cancer; FFPE clinical tissue samples; Idylla™ MSI assay; Microsatellite instability; Multi-center study.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Automation, Laboratory
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Colorectal Neoplasms / chemistry*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis*
  • Fixatives
  • Formaldehyde
  • Humans
  • Immunohistochemistry*
  • Microsatellite Instability*
  • Mutation*
  • Paraffin Embedding*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Tissue Fixation*

Substances

  • Biomarkers, Tumor
  • Fixatives
  • Formaldehyde