Idylla microsatellite instability assay versus mismatch repair immunohistochemistry: a retrospective comparison in gastric adenocarcinoma

Abstract

Up to 22% of all gastric adenocarcinomas are of the microsatellite instability (MSI) subtype. This subtype may not benefit from conventional adjuvant chemotherapy but does respond to novel immunotherapies. A proportion of MSI gastric adenocarcinomas are associated with inherited disease, inferring an opportunity to screen for further cancers in the patient while also identifying at-risk relatives. Although the importance of MSI subtyping is clear, the methods of detection vary. The main techniques are MSI testing and mismatch repair (MMR) immunohistochemistry (IHC). This study compares a novel Idylla (Biocartis) MSI assay to MMR IHC across 50 biopsies of gastric adenocarcinoma. The methods were concordant across 48 cases. The two discrepant results demonstrated known difficulties in the interpretation of IHC. Idylla MSI testing presents several advantages over MMR IHC but both methods are well established in detecting this subtype of gastric adenocarcinoma. The methods are best regarded as complementary tests, performing most optimally when combined.

Idylla MSI test combined with immunohistochemistry is a valuable and cost effective strategy to search for microsatellite instable tumors of noncolorectal origin

“…Previous studies using the Idylla MSI test have also reported discrepant results in small subsets of samples screened for dMMR/MSI using different methods, IHC and molecular ones (Idylla and non‐Idylla ones). Interestingly, in about 110 samples with discrepant results between Idylla and non‐Idylla methods, the confrontation to the dMMR/MSI result of a third method confirmed in 60 cases the result of Idylla MSI test whereas false results of this test were concluded in about 50 cases 7,9,11,13–16,18,23 . In some reports, to perform a new Idylla MSI test with another cartridge in case of an initial discrepant result between IHC and Idylla test have also resulted in different molecular results correcting the initial discrepancy 13 …”

“…5 If IHC is performed routinely in pathology laboratories, molecular analyses can be either outsourced in laboratories with molecular pathology expertise, or, more recently, diagnosed using fully-automated rapid molecular analyses accessible even to pathologists with no expertise in molecular analyses. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] The diagnostic strategies combining IHC and MSI molecular testing in the same pathology laboratory are particularly interesting because (1) by avoiding external analyses, they accelerate turnaround times for optimal subsequent treatment choices, (2) they facilitate the in-house close confrontation of the results of these two methods which can be sometimes discrepant due to some features of tumor tissues (e.g., tumor cells versus non-tumor cells contents) and/or non-perfect performances of dMMR/MSI diagnostic methods.…”

“…[9][10][11][12][13][15][16][17][18][19][20]22,23 Series of non-CRC tumors (about 1000 cases including several different organs and tumor types, as endometrial, urothelial, gastric, but also fewer duodenal-pancreatic, ovarian, prostatic, small-intestine carcinomas, or cutaneous adnexal tumors) have also reported good performances of this Idylla MSI test with nervertheless inferior sensitivity in comparison with CRC (about 92% sensitivity and 99% specificity in non-CRC tumors). [6][7][8][9]11,12,14,15,18,21,23,24 At the present time, the availability of this new test asks the question whether pathology laboratories can (1) perform themselves this Idylla MSI test without complementary external validation molecular analyses, (2) use the Idylla MSI test as a standalone test without systematic confrontation to MMR IHC, (3) implement the Idylla MSI test at a reasonable cost in routine diagnosis compared with strategies implicating external analysis. In this study, we intend to solve these questions in a real-life context of a pathology laboratory in France about a series of 54 non-CRC tumors.…”

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 ].…”

Evaluation of Micro Satellite Instability and Mismatch Repair Status in Different Solid Tumors: A Multicenter Analysis in a Real World Setting

“…Generally, the most widely adopted procedure for MSI evaluation relies on the Sanger sequencing-based Bethesda panel, which covers two mononucleotide (BAT-25 and BAT-26) and three dinucleotide (D5S346, D2S123, and D17S250) repetitions [13] or, alternatively, a panel covering five poly-A mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-24, NR-27) [14]. However, recent studies have demonstrated that the fully automated PCR high-resolution melt curve analysis (Idylla TM , Biocartis, Mechelen, Belgium) [11,[15][16][17][18][19][20][21][22][23][24][25][26] and the automated microfluidic electrophoretic run chip-based assay (TapeStation 4200, Agilent Technologies, Santa Clara, CA, USA) are easier to use, faster, and less expensive than Sanger sequencing [11,27,28].…”