Detection of microsatellite instability with Idylla MSI assay in colorectal and endometrial cancer

• Published in: Virchows Archiv : an international journal of pathology Vol. 479; no. 3; pp. 471 - 479
• Main Authors: Ukkola, Iiris, Nummela, Pirjo, Pasanen, Annukka, Kero, Mia, Lepistö, Anna, Kytölä, Soili, Bützow, Ralf, Ristimäki, Ari
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2021; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - chemistry; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA Mismatch Repair; DNA Repair Enzymes - analysis; Early Detection of Cancer; Endometrial cancer; Endometrial Neoplasms - chemistry; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Endometrium; Female; Genetic disorders; Genetic markers; Humans; Immunohistochemistry; Male; Medicine; Medicine & Public Health; Microsatellite Instability; Microsatellites; Middle Aged; Mismatch repair; MLH1 protein; MMR protein; MSH2 protein; MSH6 protein; Mutation; Original; Original Article; Pathology; Polymerase Chain Reaction; Predictive Value of Tests; Protein expression; Proteins; Reproducibility of Results; Retrospective Studies; Sensitivity analysis; Tumors; Immunohistochemistry; Idylla; Microsatellite instability; Endometrial cancer; Mismatch repair; Colorectal cancer
• ISSN: 0945-6317; 1432-2307; 1432-2307
• DOI: 10.1007/s00428-021-03082-w

Universal testing of microsatellite instability (MSI) is recommended for colorectal cancer (CRC) and endometrial cancer (EC) to screen for Lynch syndrome and to aid in assessing prognosis and optimal treatment. We compared the performance of Idylla MSI test to immunohistochemistry (IHC) of mismatch repair (MMR) proteins in consecutive series of 100 CRC and 108 EC samples, as well as in retrospective series of 28 CRC and 33 EC specimens with known deficient MMR protein expression. The concordance between the Idylla test and IHC was 100% in all CRC samples (
n
=128) but lower in EC samples (87.2%;
n
=141). In the EC samples, sensitivity of Idylla test was 72.7% and specificity 100%. EC MSI/dMMR agreement was 85.4% for MLH1, 87.5% for MSH2, and only 35.3% for MSH6. When we analyzed 14 EC samples that were discrepant, i.e., dMMR using IHC and microsatellite stable using Idylla, with microsatellite markers BAT25 and BAT26, we found four cases to be replication error (RER) positive. All RER positive cases were deficient for MSH6 protein expression. We also re-analyzed EC samples with variable tumor cellularity to determine the limit of detection of the Idylla test and found that a 30% or higher tumor cellularity is required. We conclude that Idylla MSI test offers a sensitive and specific method for CRC diagnostics but is less sensitive in EC samples especially in the case of MSH6 deficiency.