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

2021 ◽  
Author(s):  
Iiris Ukkola ◽  
Pirjo Nummela ◽  
Annukka Pasanen ◽  
Mia Kero ◽  
Anna Lepistö ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endometrial Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Limit Of Detection ◽  
Specific Method ◽  
Consecutive Series ◽  
Replication Error ◽  
Universal Testing ◽  
Mmr Proteins

AbstractUniversal testing of microsatellite instability (MSI) is recommended for colorectal cancer (CRC) and endometrial cancer (EC) to screen for Lynch syndrome and to aid in assessing prognosis and optimal treatment. We compared the performance of Idylla MSI test to immunohistochemistry (IHC) of mismatch repair (MMR) proteins in consecutive series of 100 CRC and 108 EC samples, as well as in retrospective series of 28 CRC and 33 EC specimens with known deficient MMR protein expression. The concordance between the Idylla test and IHC was 100% in all CRC samples (n=128) but lower in EC samples (87.2%; n=141). In the EC samples, sensitivity of Idylla test was 72.7% and specificity 100%. EC MSI/dMMR agreement was 85.4% for MLH1, 87.5% for MSH2, and only 35.3% for MSH6. When we analyzed 14 EC samples that were discrepant, i.e., dMMR using IHC and microsatellite stable using Idylla, with microsatellite markers BAT25 and BAT26, we found four cases to be replication error (RER) positive. All RER positive cases were deficient for MSH6 protein expression. We also re-analyzed EC samples with variable tumor cellularity to determine the limit of detection of the Idylla test and found that a 30% or higher tumor cellularity is required. We conclude that Idylla MSI test offers a sensitive and specific method for CRC diagnostics but is less sensitive in EC samples especially in the case of MSH6 deficiency.

scholarly journals Detection of Mismatch Repair and Microsatellite Instability in Colorectal Cancer Patients

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Muhammad Ishaque Faizee
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Poor Response ◽  
Protein Product ◽  
Mismatch Repair Proteins ◽  
Altered Gene ◽  
Colorectal Cancer Patients ◽  
Mmr Proteins

Introduction:  Colorectal cancer is the third most common cancer worldwide. Microsatellite instability (MSI) contributes to be one of the main mechanisms in colorectal cancer. Individuals with MSI tumors have loss of expression of one or more Mismatch Repair proteins. MSI tumors have better survival rate than microsatellite stable (MSS) tumors, poor response to 5FU-based adjuvant chemotherapy and relatively successful immunotherapy in metastatic MSI tumors. Immunohistochemistry recognizes altered gene by recognizing loss of its protein product. Based on the presence or absence of Mismatch repair proteins, groups are classified into Mismatch repair proficient (MMR-p) and Mismatch repair deficient (MMR-d).  Aim:  To investigate the immunohistochemical profile of Mismatch repair proteins namely: hMLH1, hMSH2, hMSH6, and hPMS2 in surgically resected colorectal cancer specimens.  Materials and Method:  A total of 76 cases were selected from the Histopathology Department of HTAA to determine MMR protein expression status. Cases were either MMR-p or MMR-d. Results:  Of the specimens which were properly immunostained, seventeen out of seventy-six cases (22.37%) showed loss of one or more MMR proteins expression and thus were MMR-d. MLH1, MSH2, MSH6 and PMS2 protein expression was detected as 85.53% (65/76), 81.6% (62/76), 88.16% (67/76), and 76.32% (58/76), respectively. Conclusion: Mismatch repair proteins profile should be done using immunohistochemistry in  local laboratories on these selected cases before referring for the expensive molecular test.

Microsatellite instability evaluation: which test to use for endometrial cancer?

2021 ◽  
pp. jclinpath-2021-207723
Author(s):  
Paola Rafaniello-Raviele ◽  
Ilaria Betella ◽  
Alessandra Rappa ◽  
Davide Vacirca ◽  
Gianluca Tolva ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Microsatellite Instability ◽  
Automated System ◽  
Tissue Samples ◽  
Valuable Alternative ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed ◽  
Mmr Proteins

AimsAnalysis of microsatellite instability (MSI) is strongly recommended in endometrial cancer (EC) and colorectal cancer to screen for Lynch syndrome, to predict prognosis and to determine optimal treatment and follow-up. In a large monoinstitutional series of ECs, we evaluated the reliability and accuracy of Idylla assay, a rapid, fully automated system to detect MSI, and we compared its performance with two routine reference methods.MethodsWe evaluated MSI status in 174 formalin-fixed, paraffin-embedded EC tissue samples using immunohistochemistry (IHC) for mismatch repair (MMR) proteins and Idylla assay. Samples with discordant or equivocal results were analysed with a third technique, the Promega MSI kit.ResultsIdylla MSI assay and IHC were highly concordant (overall agreement: 154/170=90.59%, 95% CI 85.26% to 94.12%). However, in four samples, MMR-IHC staining was equivocal; moreover, 16 cases showed discordant results, that is, MMR deficient using IHC and microsatellite stable using Idylla. These 20 samples were reanalysed using the MSI-Promega kit, which showed the same results of Idylla assay in 18/20 cases (overall agreement: 90%, 95% CI 69.90% to 97.21%).ConclusionsOur results suggest that IHC is an efficient method to determine MMR status in ECs. However, the Idylla MSI assay is a rapid and reliable tool to define MSI status, and it could represent a valuable alternative to conventional MSI-PCR methods.

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

2021 ◽  
pp. jclinpath-2021-207606
Author(s):  
Loëtitia Favre ◽  
Ruiqian Chen ◽  
Yaëlle Bellahsen-Harrar ◽  
Nicolas Ortonne ◽  
Anaïs Pujals
Keyword(s):  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Sensitivity And Specificity ◽  
Molecular Techniques ◽  
Molecular Methods ◽  
Specific Method ◽  
Skin Tumours ◽  
Automated Method ◽  
Mmr Deficiency ◽  
Mmr Proteins

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.

Low Microsatellite Instability Is Associated With Poor Prognosis in Stage C Colon Cancer

2005 ◽  
Vol 23 (10) ◽  
pp. 2318-2324 ◽  
Author(s):  
Maija R.J. Kohonen-Corish ◽  
Joseph J. Daniel ◽  
Charles Chan ◽  
Betty P.C. Lin ◽  
Sun Young Kwun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
Dna Methyltransferase ◽  
Prognostic Significance ◽  
Promoter Hypermethylation ◽  
Prognostic Indicator ◽  
Study Cohort ◽  
Distinct Subgroup

Purpose The significance of low microsatellite instability (MSI-L) in colorectal cancer is poorly understood. No clear biologic distinction has been found between MSI-L and microsatellite stable (MSS) colorectal cancer, and these two phenotypes are usually combined when analyzed against the well-defined high MSI (MSI-H) phenotype. Evidence is emerging that an O6-methylguanine DNA methyltransferase (MGMT) gene defect is associated with MSI-L. Therefore, to further define this phenotype, we undertook a detailed analysis of the prognostic significance of MSI-L and loss of MGMT expression in colon cancer. Patients and Methods The study cohort was 183 patients with clinicopathologic stage C colon cancer who had not received adjuvant therapy. We analyzed MSI status, MGMT, and mismatch repair protein expression, as well as MGMT and p16 promoter hypermethylation. Results We showed that MSI-L defines a group of patients with poorer survival (P = .026) than MSS patients, and that MSI-L was an independent prognostic indicator (P = .005) in stage C colon cancer. Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival. Conclusion MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.

Loss of Expression of DNA Mismatch Repair Proteins Is Rare in Pancreatic and Small Intestinal Neuroendocrine Tumors

2011 ◽  
Vol 135 (12) ◽  
pp. 1539-1544 ◽  
Author(s):  
Thomas Arnason ◽  
Heidi L Sapp ◽  
Daniel Rayson ◽  
Penelope J Barnes ◽  
Magdalena Drewniak ◽  
...  
Keyword(s):  
Protein Expression ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Neuroendocrine Tumors ◽  
Dna Mismatch Repair ◽  
High Rate ◽  
Dna Mismatch ◽  
Small Intestinal ◽  
Msi Analysis ◽  
Mmr Proteins

Context.—Two recent studies have identified a high rate of microsatellite instability (MSI) in pancreatic neuroendocrine tumors (pNETs). Microsatellite instability is rare in small intestinal neuroendocrine tumors (NETs). It is unclear why there is discordance in the frequency of MSI in the 2 studies of pNETs and why this mechanism is comparatively rare in small intestinal tumors. Loss of expression of DNA mismatch repair (MMR) proteins, which is known to correlate strongly with MSI, is not well studied in pancreatic or small intestinal NETs. Objective.—To determine if there is loss of expression of MMR protein expression in pancreatic or small intestinal NETs. Design.—Sixty-nine patients (31 male, 38 female; mean age, 59.2 years) were identified who had a resection for a primary pancreatic (n  =  35) or primary small intestinal (n  =  34) NET during an 18-year period. Immunohistochemical stains for MLH1, MSH2, MSH6, and PMS2 were applied to archived tissue from all cases. All pNETs with adequate tissue (n  =  32) were also assessed by MSI analysis. Results.—There was preserved expression of MLH1, MSH2, MSH6, and PMS2 in all 35 pNETs. Of 32 pNETs tested by polymerase chain reaction, 28 were microsatellite stable and DNA did not amplify in 4. In 34 small intestinal NETs, 2 cases had indeterminate MLH1 and 1 case had indeterminate PMS2 expression. The remainder had intact MMR protein expression. Conclusion.—Defects in DNA MMR proteins are rare in pancreatic and small intestinal NETs, raising doubt that MSI plays a significant role in the pathogenesis of these tumors.

Distinctive patterns of p53 protein expression and microsatellite instability in human colorectal cancer

2011 ◽  
Vol 42 (12) ◽  
pp. 1897-1910 ◽  
Author(s):  
Christine Nyiraneza ◽  
Anne Jouret-Mourin ◽  
Alex Kartheuser ◽  
Philippe Camby ◽  
Olivier Plomteux ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Microsatellite Instability ◽  
P53 Protein ◽  
Human Colorectal Cancer ◽  
P53 Protein Expression
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