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

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.

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

“…They also demonstrated SEC31A to be a gene with no extreme specificity to harbor frameshift MSI in either CRC or EC genomes. Further, the multicenter Idylla MSI test study of CRC reported ACVR2A to be the most often mutated biomarker (94.0%) and SEC31A to be the least mutated marker (60.9%) [11], and our frequencies are in line with a sequencing study demonstrating ACVR2A mutations in 92% and SEC31A mutations in 54% of one hundred MSI CRC cases [27].…”

“…In this report, one case was MSS in Idylla analysis, whereas IHC was dMMR and Promega MSI analysis was MSI and interestingly tumor mutation burden was very high, whereas three IHC dMMR cases showed MSS in DNA-based assays and low tumor mutation burden. In addition, a multi-center real-life global study including 44 clinical centers and 1301 CRC samples showed the concordance level between the Idylla test and IHC to be as high as 96.4%, with Idylla having lower failure rates [11].…”

“…One novel way to assess the MSI status is Idylla MSI test, which analyzes a panel of seven monomorphic microsatellite biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, and SULF2) using fluorescent-labeled molecular beacons combined with PCR amplification. Idylla test is an automatic system performing all the necessary steps from a formalin-fixed paraffin-embedded (FFPE) tissue flake to MSI status information, including DNA extraction, amplification, and data analysis in 150 min [11].…”

Detection of Microsatellite Instability: State of the Art and Future Applications in Circulating Tumour DNA (ctDNA)

“…The Idylla ® MSI assay (Bioartis, NV, Mechelen, Belgium) is a fully-automated PCR-based system that comprises the analysis of seven novel monomorphic homopolymer regions ( ACVR2A , BTBD7 , DIDO1 , MRE11 , RYR3 , SEC31A , SULF2 ) in a single-use cartridge with all reagents on board ( Table 2 ) [ 74 ]. In colorectal, endometrial, and gastric cancers, the Idylla ® system provides a high concordance (>96%) and lower failure rate compared to the standard reference methods [ 75 , 76 , 77 , 78 ]. Less is known about its performance in other cancers and further studies are needed to confirm its interest in such cases [ 79 ].…”

Low Concordance Between T-Cell Densities in Matched Primary Tumors and Liver Metastases in Microsatellite Stable Colorectal Cancer

“…The Idylla™ MSI Assay from Biocartis (Mechelen, Belgium) was used according to the manufacturer’s instructions to determine whether tumors were MSS or MSI ( 23 ). In 35 of the 58 cases, isolated DNA was available from CLM samples as previously described ( 7 ), while in 23 cases, FFPE tissue was used [from CLM resection sample (n = 20) or from the pCRC sample (n = 3)].…”