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Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer.

ABSTRACT: DNA mismatch repair deficiency (dMMR) testing is crucial for diagnosing Lynch syndrome and detection of microsatellite unstable (MSI) tumors eligible for immunotherapy. The aim of this study was to compare the relative diagnostic performance of three molecular MSI assays: polymerase chain reaction (PCR), MSI testing by Idylla and next-generation-sequencing (NGS) on 49 tumor samples (28 colorectal and 21 endometrial adenocarcinomas) versus immunohistochemistry (IHC). Discrepancies were investigated by MLH1 methylation analysis and integrated with germline results if available. Overall, the molecular assays achieved equivalent diagnostic performance for MSI detection with area under the ROC curves (AUC) of respectively 0.91 for Idylla and PCR, and 0.93 for NGS. In colorectal cancers with tumor cell percentages ≥ 30% all three molecular assays achieved 100% sensitivity and specificity (AUC = 1) versus IHC. Also, in endometrial cancers, all three molecular assays showed equivalent diagnostic performance, albeit at a clearly lower sensitivity ranging from 58% for Idylla to 75% for NGS, corresponding to negative predictive values from 78 to 86%. PCR, Idylla and NGS show similar diagnostic performance for dMMR detection in colorectal and endometrial cancers. Molecular MSI analysis has lower sensitivity for dMMR detection in endometrial cancer indicating that combined use of both IHC and molecular methods is recommended.Clinical Trial Number/IRB: B1172020000040, Ethical Committee, AZ Delta General Hospital.

SUBMITTER: Dedeurwaerdere F

PROVIDER: S-EPMC8213758 | biostudies-literature |

REPOSITORIES: biostudies-literature

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

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The landscape of microsatellite instability in colorectal and endometrial cancer genomes.

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Subtyping of microsatellite instability-high colorectal cancer.

Project description:BACKGROUND:Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis than patients with microsatellite stable (MSS) CRC. However, some MSI-H CRC patients do not gain overall survival benefits from immune checkpoint-blockade treatment. In other words, heterogeneity within the subgroup of MSI-H tumors remains poorly understood. Thus, an in-depth molecular characterization of MSI-H tumors is urgently required. METHODS:Here, we use nonnegative matrix factorization (NMF)-based consensus clustering to define CRC MSI-H subtypes in The Cancer Genome Atlas and a French multicenter cohort GSE39582. CIBERSORT was used to calculate the proportions of 22 lymphocytes in tumor tissue in MSI-H subtypes. RESULTS:MSI-H CRC samples basically clustered into two subgroups (MSI-H1 and MSI-H2). MSI-H1 was characterized by a lower BRAF mutational status, higher frequency of chromosomal instability, global hypomethylation, and worse survival than MSI-H2. Further examination of the immune landscape showed that macrophages of the M2 phenotype were enriched in MSI-H1, which may be associated with poor prognosis in this subgroup. CONCLUSIONS:Our results illustrate the genetic heterogeneity in MSI-H CRCs and macrophages may serve as good targets for anticancer therapy in MSI-H1.

| S-EPMC6647262 | biostudies-literature

Role of detection of microsatellite instability in Chinese with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer.

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