Comparison of the Idylla™ MSI assay with the Promega™ MSI Analysis System and immunohistochemistry on formalin-fixed paraffin-embedded tissue of endometrial carcinoma: results from an international, multicenter study

Gatius, Sònia; Velasco, Ana; Varela, Mar; Cuatrecasas, Míriam; Jares, Pedro; Setaffy, Lisa; Bonhomme, Benjamin; Santón, Almudena; Lindemann, Kristina; Croce, Sabrina; Davidson, Ben; Lax, Sigurd; Palacios, José; Matías‐Guiu, Xavier

doi:10.1007/s00428-022-03291-x

Cited by 9 publications

(2 citation statements)

References 31 publications

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“…Ferguson et al made comparisons in the MMR subgroups and reported that 21% of the IHC dMMR tumors were MSS via PCR [40]. In enriched dMMR population studies with an overrepresentation of dMMR cases, discrepancies of more than 10% have been reported between IHC and PCR, which are in line with our results [36,41].…”

Section: Discussionsupporting

confidence: 89%

Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer

Mendiola,

Heredia-Soto,

Ruz-Caracuel

et al. 2023

IJMS

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Approximately 20–30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC.

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Section: Discussionsupporting

confidence: 89%

Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer

Mendiola,

Heredia-Soto,

Ruz-Caracuel

et al. 2023

IJMS

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“…The accurate determination of mismatch repair deficiency is obviously of critical importance. Several studies have addressed the issue of concordance [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ] between MSI and IHC for assessing mismatch repair deficiency. However, there are a limited number of studies [ 13 , 28 , 29 , 30 , 31 , 34 ] that also take into account somatic gene mutations.…”

Section: Introductionmentioning

confidence: 99%

Clinical Testing for Mismatch Repair in Neoplasms Using Multiple Laboratory Methods

Yang

Chen

Roy‐Chowdhuri

et al. 2022

Cancers

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Background: A deficiency in DNA mismatch repair function in neoplasms can be assessed by an immunohistochemical (IHC) analysis of the deficiency/loss of the mismatch repair proteins (dMMR) or by PCR-based methods to assess high microsatellite instability (MSI-H). In some cases, however, there is a discrepancy between the IHC and MSI analyses. Several studies have addressed the issue of discrepancy between IHC and MSI deficiency assessment, but there are limited studies that also incorporate genetic/epigenetic alterations. Methods: In this single-institution retrospective chart-review study, we reviewed 706 neoplasms assessed between 2015 and 2021. All eligible neoplasms were assessed by IHC testing, MSI analysis by PCR-based assay, and tumor-normal paired next-generation sequencing (NGS) analysis. Eighty percent of neoplasms with MLH1 protein loss had a concurrent MLH1 promoter methylation analysis. Mutation data for MMR genes, IHC, MSI analysis, and tumor histology were correlated with each other. Results: Fifty-eight (8.2%) of 706 neoplasms had MSI-H by PCR and/or dMMR by IHC. Of the 706 analyzed neoplasms, 688 neoplasms (98%) had concordant results: MSI-H/dMMR (n = 44), microsatellite-stable (MSS)/proficient MMR (pMMR) (n = 625), and MSI-Low (L)/pMMR (n = 19). Of the remaining 18 neoplasms, 9 had a major discordance: MSS/loss of MSH2 and MSH6 (n = 3), MSS/loss of MSH6 (n = 2), MSS/Loss of MLH1 and PMS2 (n = 1), and MSI-High/pMMR (n = 3). In total, 57% of cases with dMMR and 61% of cases with MSI-H had a null mutation of an MMR gene mutation (or methylation of the MLH1 promoter), whereas this figure was 1% for neoplasms with a normal IHC or MSI pattern (p < 0.001). Among 9 cases with major discordance between MSI and IHC, only 3 cases (33%) had an underlying genetic/epigenetic etiology, whereas 37 (76%) of 49 cases with MSI-H and/or dMMR and without major discordance had an underlying genetic abnormality (p = 0.02). Discussion: For most neoplasms, IHC and PCR-based MSI testing results are concordant. In addition, an underlying genetic abnormality (a null mutation of an MMR gene or MLH1 promoter methylation) was attributable to dMMR and/or MSI-H findings. For neoplasms with major discordance in IHC and MSI testing, the addition and integration of NGS results and MLH1 promoter methylation analyses can be beneficial for resolving borderline cases, thereby facilitating patient management.

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Enhanced Commendable Sensitivity and Specificity for MSI in Colorectal Cancer by a New PCR‐HRM Based 8‐Loci MSI Assay

Xiang,

Ma,

Ying

et al. 2024

Clinical Laboratory Analysis

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BackgroundThis study evaluated the performance of the PCR‐HRM assay by comparing it with immunohistochemistry (IHC) for mismatch repair (MMR) proteins and the PCR capillary electrophoresis (PCR‐CE) methods.ResultsA total of 224 patients with colorectal cancer participated in the study, with nearly half having mismatch repair deficiency (dMMR) tissues and the remainder possessing pMMR tissues. There was a 97.77% concordance between the PCR‐HRM assay and IHC, and a 97.56% concordance between PCR‐HRM and the PCR‐CE assay. In comparison with IHC for dMMR proteins, the PCR‐HRM demonstrated a sensitivity of 96.36% and a specificity of 99.12%. When juxtaposed with the PCR‐CE assay, its sensitivity was 98.96% and specificity stood at 96.33%. The mutations observed in the microsatellite loci were uniformly distributed across all eight loci. Discrepant outcomes were more frequent in instances of MLH1 and PMS2 deficiency. Furthermore, the germline mutation status of MLH1, MSH2, PMS2, and MSH6 in 62 patients was ascertained using next‐generation sequencing. All patients displaying MMR gene pathogenic mutations (N = 14) were identified as MSI‐H by PCR‐HRM, whereas those with MSS tissues (N = 43) did not exhibit MMR gene pathogenic mutations. Thus, the PCR‐HRM method proficiently pinpoints tumors with verified germline MMR mutations, indicative of Lynch syndrome.ConclusionConclusively, the PCR‐HRM assay emerges as a swift and congruent diagnostic tool for microsatellite instability, boasting commendable sensitivity and specificity in colorectal cancer.

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Comparison of the Idylla™ MSI assay with the Promega™ MSI Analysis System and immunohistochemistry on formalin-fixed paraffin-embedded tissue of endometrial carcinoma: results from an international, multicenter study

Cited by 9 publications

References 31 publications

Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer

Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer

Clinical Testing for Mismatch Repair in Neoplasms Using Multiple Laboratory Methods

Enhanced Commendable Sensitivity and Specificity for MSI in Colorectal Cancer by a New PCR‐HRM Based 8‐Loci MSI Assay

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