Endometrial Cancer and Molecular Methods: A Case Study of MSI Heterogeneity based on Metastatic Location with IdyllaTM

Abstract

Abstract Introduction/Objective MMR deficiency (dMMR) and Microsatellite Instability (MSI) are hallmarks of not only Lynch Syndrome and Colorectal Cancer (CRC), but Endometrial cancer. Endometrial cancer is the most common female gynecological cancer, yet molecular tests for MSI often focus solely on CRC validation. MSI in Endometrial cancer correlates with higher staging and more aggressive pathology, resulting in a need for reliable testing methods. Immunohistochemistry (IHC) staining is the current standard for MSI detection, due to the known association between dMMR and MSI-H. Direct detection of MSI requires molecular methods, however, there is a lack of standardization of protocol between labs. Idylla™ (Biocartis, Jersey City, NJ), an automated cartridge-based PCR assay, could help eliminate this ambiguity. Methods/Case Report To determine whether the Idylla™ MSI assay can be reliably used to detect MSI in Endometrial cancers, both primary and metastatic sites for two known MSI-H patients were examined using the Idylla ™ MSI assay and an IHC MMR panel (MLH1, MSH2, MSH6, PMS2). Results (if a Case Study enter NA) The results showed MSI-H for both patients uterine primary sites on the Idylla™. Examination of the Idylla™ results for metastatic sites found they contradicted the IHC panel results for some sites. Idylla™ produced expected results for the omentum and intestinal metastases in patient IN-20-1. The Idylla™ results for the ovarian and abdominal metastatic lesions in patient IN-15/17-2 directly contradicted the MMR findings and the MSI-H result provided for the uterine primary site. Conclusion This discrepancy between primary and metastatic site results is likely due to MSI heterogeneity in these metastatic lesions than test errors. At this time, it is not recommended to use the Idylla™ MSI test for Endometrial cancers, particularly those with abdominal or ovarian metastasis. Further testing will be needed to verify if intestinal metastatic sites are consistently MSI-H. IHC should remain the prime mode of detection for possible dMMR MSI-H Endometrial tumors until an assay catered specifically towards Endometrial cancers is made.