Universität zu Köln

Siemanowski, Janna, Schoemig-Markiefka, Birgid, Buhl, Theresa, Haak, Anja, Siebolts, Udo ORCID: 0000-0002-7463-9195, Dietmaier, Wolfgang, Arens, Norbert, Pauly, Nina, Ataseven, Beyhan ORCID: 0000-0002-2823-7590, Buettner, Reinhard and Merkelbach-Bruse, Sabine (2021). Managing Difficulties of Microsatellite Instability Testing in Endometrial Cancer-Limitations and Advantages of Four Different PCR-Based Approaches. Cancers, 13 (6). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary Due to the approval of immune checkpoint inhibitor therapy for microsatellite instability-high or mismatch repair-deficient advanced solid tumors, testing of both biomarkers has gained interest in recent years. Available testing systems were established in the context of Lynch Syndrome for colorectal cancer, thus differences between microsatellite profiles across cancer types may lead to false data interpretation using validated tests for another tumor entity. The present study deals with challenges during microsatellite instability testing in endometrial cancer (EC) and provides a comprehensive comparative study of four different PCR-based approaches which could help to improve microsatellite instability (MSI) testing in future screenings. A validation strategy has been developed for the Idylla system, which can guide the method transfer to other tumor entities, and a screening procedure for EC has been proposed. By direct comparison, this study was able to highlight advantages and limitations of each system in an extensive manner. Microsatellite instability (MSI), a common alteration in endometrial cancers (EC) is known as a biomarker for immune checkpoint therapy response alongside screening for Lynch Syndrome (LS). However, former studies described challenging MSI profiles in EC hindering analysis by using MSI testing methods intensively validated for colorectal cancer (CRC) only. In order to reduce false negatives, this study examined four different PCR-based approaches for MSI testing using 25 EC samples already tested for mismatch repair deficiency (dMMR). In a follow up validation set of 75 EC samples previously tested both for MMR and MSI, the efficiency of a seven-marker system corresponding to the Idylla system was further analyzed. Both Bethesda and Promega marker panels require trained operators to overcome interpretation complexities caused by either hardly visible additional peaks of one and two nucleotides, or small shifts in microsatellite repeat length. Using parallel sequencing adjustment of bioinformatics is needed. Applying the Idylla MSI assay, an evaluation of input material is more crucial for reliable results and is indispensable. Following MMR deficiency testing as a first-line screening procedure, additional testing with a PCR-based method is necessary if inconclusive staining of immunohistochemistry (IHC) must be clarified.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Siemanowski, Janna UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoemig-Markiefka, Birgid UNSPECIFIED UNSPECIFIED UNSPECIFIED Buhl, Theresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Haak, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Siebolts, Udo UNSPECIFIED orcid.org/0000-0002-7463-9195 UNSPECIFIED Dietmaier, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Arens, Norbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Pauly, Nina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ataseven, Beyhan UNSPECIFIED orcid.org/0000-0002-2823-7590 UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-589976
DOI:	10.3390/cancers13061268
Journal or Publication Title:	Cancers
Volume:	13
Number:	6
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA MISMATCH REPAIR; MUTATION; TUMORS; PROFILES; PATTERNS; HOMOLOG; MSH6 Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58997