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Managing Difficulties of Microsatellite Instability Testing in Endometrial Cancer-Limitations and Advantages of Four Different PCR-Based Approaches

1
Institute of Pathology, University Hospital Cologne, D-50924 Cologne, Germany
2
Institute of Pathology, University Hospital Halle (Saale), D-06112 Halle, Germany
3
Institute of Pathology, University Regensburg, D-93053 Regensburg, Germany
4
Center for Histology, Cytology and Molecular Diagnostics Trier, D-54296 Trier, Germany
5
Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, D-45136 Essen, Germany
6
Department of Obstetrics and Gynecology, University Hospital, LMU Munich, D-81377 Munich, Germany
*
Author to whom correspondence should be addressed.
These two authors contributed equally to the present manuscript.
Academic Editor: Andrzej Semczuk
Cancers 2021, 13(6), 1268; https://doi.org/10.3390/cancers13061268
Received: 17 February 2021 / Accepted: 10 March 2021 / Published: 12 March 2021
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. View Full-Text
Keywords: microsatellite instability; mismatch repair deficiency; polymerase chain reaction; immunohistochemistry; endometrial cancer microsatellite instability; mismatch repair deficiency; polymerase chain reaction; immunohistochemistry; endometrial cancer
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MDPI and ACS Style

Siemanowski, J.; Schömig-Markiefka, B.; Buhl, T.; Haak, A.; Siebolts, U.; Dietmaier, W.; Arens, N.; Pauly, N.; Ataseven, B.; Büttner, R.; Merkelbach-Bruse, S. Managing Difficulties of Microsatellite Instability Testing in Endometrial Cancer-Limitations and Advantages of Four Different PCR-Based Approaches. Cancers 2021, 13, 1268. https://doi.org/10.3390/cancers13061268

AMA Style

Siemanowski J, Schömig-Markiefka B, Buhl T, Haak A, Siebolts U, Dietmaier W, Arens N, Pauly N, Ataseven B, Büttner R, Merkelbach-Bruse S. Managing Difficulties of Microsatellite Instability Testing in Endometrial Cancer-Limitations and Advantages of Four Different PCR-Based Approaches. Cancers. 2021; 13(6):1268. https://doi.org/10.3390/cancers13061268

Chicago/Turabian Style

Siemanowski, Janna, Birgid Schömig-Markiefka, Theresa Buhl, Anja Haak, Udo Siebolts, Wolfgang Dietmaier, Norbert Arens, Nina Pauly, Beyhan Ataseven, Reinhard Büttner, and Sabine Merkelbach-Bruse. 2021. "Managing Difficulties of Microsatellite Instability Testing in Endometrial Cancer-Limitations and Advantages of Four Different PCR-Based Approaches" Cancers 13, no. 6: 1268. https://doi.org/10.3390/cancers13061268

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