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 r...

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Autores principales:	Franceska Dedeurwaerdere, Kathleen BM Claes, Jo Van Dorpe, Isabelle Rottiers, Joni Van der Meulen, Joke Breyne, Koen Swaerts, Geert Martens
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e513393128942018dcc7c80a00264c0
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spelling	oai:doaj.org-article:0e513393128942018dcc7c80a00264c02021-12-02T16:04:26ZComparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer10.1038/s41598-021-91974-x2045-2322https://doaj.org/article/0e513393128942018dcc7c80a00264c02021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91974-xhttps://doaj.org/toc/2045-2322Abstract 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.Franceska DedeurwaerdereKathleen BM ClaesJo Van DorpeIsabelle RottiersJoni Van der MeulenJoke BreyneKoen SwaertsGeert MartensNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Franceska Dedeurwaerdere Kathleen BM Claes Jo Van Dorpe Isabelle Rottiers Joni Van der Meulen Joke Breyne Koen Swaerts Geert Martens Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer
description	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.
format	article
author	Franceska Dedeurwaerdere Kathleen BM Claes Jo Van Dorpe Isabelle Rottiers Joni Van der Meulen Joke Breyne Koen Swaerts Geert Martens
author_facet	Franceska Dedeurwaerdere Kathleen BM Claes Jo Van Dorpe Isabelle Rottiers Joni Van der Meulen Joke Breyne Koen Swaerts Geert Martens
author_sort	Franceska Dedeurwaerdere
title	Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer
title_short	Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer
title_full	Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer
title_fullStr	Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer
title_full_unstemmed	Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer
title_sort	comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0e513393128942018dcc7c80a00264c0
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_version_	1718385190662832128

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

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