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

Cancers

Norbert Arens¹  Beyhan Ataseven²  Nina Pauly²  Reinhard Büttner³  Birgid Schömig-Markiefka³  Theresa Buhl³  Sabine Merkelbach-Bruse³  Janna Siemanowski³  Udo Siebolts⁴  Anja Haak⁴  Wolfgang Dietmaier⁵ 

[1] Center for Histology, Cytology and Molecular Diagnostics Trier, D-54296 Trier, Germany;Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, D-45136 Essen, Germany;Institute of Pathology, University Hospital Cologne, D-50924 Cologne, Germany;Institute of Pathology, University Hospital Halle (Saale), D-06112 Halle, Germany;Institute of Pathology, University Regensburg, D-93053 Regensburg, Germany;

关键词: microsatellite instability;    mismatch repair deficiency;    polymerase chain reaction;    immunohistochemistry;    endometrial cancer;   

DOI  :  10.3390/cancers13061268

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown