Idylla MSI test as a new tool for microsatellite instability detection in sebaceous tumours and keratoacanthomas

Abstract

AimSebaceous tumours and keratoacanthomas can be associated with mismatch repair (MMR) deficiency and thus microsatellite instability (MSI). In such tumours, MSI phenotype could be an argument to search for an underlying Muir-Torre syndrome (MTS). MTS has been recognised as a variant of Lynch syndrome, characterised by a deficiency of the MMR proteins. In Lynch syndrome, the sensitivity and specificity of the techniques used to detect MSI is well described, which is not the case for skin tumours. In our hands, immunohistochemistry is a sensitive and specific method to detect MMR deficiency in those tumours. Contrasting with tumours of Lynch spectrum, sensitivity and specificity of molecular methods has not been extensively studied. This study aimed at evaluating two molecular methods to detect MSI phenotype in MTS associated tumours: a commonly used pentaplex PCR using Bethesda markers and the fully automated method using the Idylla MSI assay.MethodsA comparison between PCR, and Idylla was performed on 39 DNA extracted from cutaneous tumours. Immunohistochemistry was used as the gold standard to calculate sensitivity and specificity of both molecular techniques.ResultsConcordant results were found in 32 cases (82%) with pentaplex PCR and in 36 cases (92%) with Idylla. The sensitivity of pentaplex PCR to detect MSI phenotype was 76% whereas Idylla sensitivity was 90%.ConclusionIdylla is more performant than PCR, for the detection of MSI in MTS-associated tumours and is a reliable additional technique to help detecting MTS in these tumours.

Assessing and Evaluating the Scope and Constraints of Idylla Molecular Assays by Using Different Source Materials in Routine Diagnostic Settings

“…For sample type B (HE-stained tissue material), only two out of the seven systems were detected as unstable. This study is in accordance with recent studies indicating that different source materials have been proven effective in successful findings of the Idylla MSI assays and also supporting the evidence of the use of the IVD MSI assays for different solid tumor types other than CRC [ 8 , 23 , 24 , 25 ]. One unanticipated finding was that for sample type B, the number of mutated/valid microsatellites detected and the number of biomarkers amplified was less than the other sample types, for example, cases #21 and #24.…”

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

“…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.…”

Germline Testing of Mismatch Repair Genes Is Needed in the Initial Evaluation of Patients With Muir-Torre Syndrome-Associated Cutaneous Sebaceous Neoplasms: A Case Series

“…They utilize immunohistochemistry staining, microsatellite instability testing, and next-generation sequencing of the paraffin-embedded tumor. In addition, blood, saliva, or normal skin can be used for germline evaluation [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

“…Microsatellite instability occurs when mutations in mismatch repair genes result in altered gene products and either insertions or deletions in the deoxyribonucleic acid microsatellites; this makes the microsatellites either abnormally long or short. Microsatellite instability initially causes mutations of oncogenes and tumor suppressor genes; subsequently, these result in carcinogenesis [ 8 , 9 ].…”