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• W4387402169 abstract "Determination of MMR functioning in EC is recommended by international guidelines. Its deficiency leads to MSI with intermediate prognosis. Available data have shown a reasonable concordance between IHC-MMR and NGS-MSI. We aim at evaluating the sensitivity and specificity of NGS-MSI obtained from a comprehensive cancer genome profiling (CGP) assay compared with the gold standard IHC-MMR. Selected EC patients were profiled using TruSight Oncology500 High Throughput solution. MSI status was determined by 130 noncoding homopolymer regions and at least 40 sites were assessed to provide a score (threshold MSI high>20). IHC-MMR evaluation was collected from standard pathology report. From March 2022 to May 2023, 404 EC were enrolled. NGS-MSI evaluation was available for 354 (87%; see table). Cohort characteristics are reported in the table. Sensitivity and specificity of NGS-MSI testing compared to IHC-MMR were 99% (n=223/224) and 52% (n= 68/130) respectively, with a concordance rate of 82% (Cohen Kappa = 0.58; p < .0001). The positive predictive value of NGS-MSI was 78% (n=223/285), while the negative predictive value was 99% (n= 68/69). Among the 62 misclassified cases, 19 were MSH6 + MSH2 deficient, 42 MLH1 + PMS2 deficient and 1 was deficient for PMS2, MLH1 and MSH6. 38 MLH1 + PMS2 deficient patients were addressed to MLH1 promoter methylation analysis: results are available for 15 cases (11 hypermethylated, 2 partially hypermethylated). All 19 MSH6 + MSH2 deficient were addressed to genetic counselling: results are available only for 3 patient (1 displaying a MSH2 pathogenic variant).Table: 96PCharacteristicsCohort (N = 354)Histotype, n (%)Endometrioid307 (87%)Serous carcinoma18 (5%)Others29 (8%)FIGO Stage 2019*, n (%)I-II149 (93%)III-IV25 (7%)MSI status, n (%)MSI69 (19%)MSS285 (81%)MMR IHC status, n (%)pMMR224 (63%)dMMR130 (37%) Open table in a new tab . A moderate concordance between IHC-MMR and NGS-MSI was reported in our study. However, given the approval of immunotherapy in several settings it is important to further characterize the misclassified cases." @default.
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• W4387402169 date "2023-10-01" @default.
• W4387402169 modified "2023-10-07" @default.
• W4387402169 title "96P Analysis of concordance between microsatellite instability by next generation sequencing (NGS-MSI) and mismatch repair deficiency by immunohistochemistry (IHC-MMR) in endometrial cancer (EC) patients" @default.
• W4387402169 doi "https://doi.org/10.1016/j.esmoop.2023.101906" @default.
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