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Updated: May 24, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Detection of Microsatellite Instability in Endometrial Carcinoma Using a Novel Homopolymer Assay
Catherine M Nicka1, Donald C Green1, Gregory J Tsongalis1,2,3
1Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Abstract:
Approximately 30% of endometrial cancers are associated with microsatellite instability (MSI) caused by deficiencies in the DNA mismatch repair (MMR) genes (dMMR). MMR testing by immunohistochemistry for MMR proteins and MSI testing by polymerase chain reaction (PCR) are routinely utilized to screen patients with colorectal cancer and endometrial cancer for Lynch syndrome and, more recently, to identify patients eligible for immunotherapy. The Biocartis Idylla™ MSI assay is a fully automated, cartridge-based real-time PCR assay. The assay uses as little as one formalin-fixed paraffin-embedded (FFPE) tumor section and is designed to detect seven novel MSI biomarkers consisting of short homopolymers located in ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A and SULF2 genes. Mutation in two of these markers is considered MSI-H. FFPE of 35 ECs (25 dMMR and 10 microsatellite stable (MSS)) were used in this study. When tumor content was ≤20% on a slide, macrodissection was performed. The overall percent agreement with MMR IHC was 97% (31/32) with sensitivity = 96% and specificity = 100%. Pre-analytic evaluation of the manufacturer's recommended 20% tumor content cut-off is essential to ensure valid results. The Idylla MSI assay offers several advantages over other PCR-based assays including minimal hands-on time, rapid turn-around-time, no requirement for a paired normal sample and the use of FFPE directly without an extraction step.
Insights
The Idylla MSI assay accurately detects microsatellite instability (MSI) in endometrial cancer (EC) using formalin-fixed paraffin-embedded (FFPE) tissue. This automated test shows high agreement with MMR IHC, offering a rapid and efficient diagnostic tool.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Microsatellite instability (MSI) is present in about 30% of endometrial cancers (ECs) due to DNA mismatch repair (MMR) gene deficiencies.
- MMR and MSI testing are crucial for diagnosing Lynch syndrome and identifying patients eligible for immunotherapy.
- Current testing methods include immunohistochemistry (IHC) for MMR proteins and polymerase chain reaction (PCR) for MSI.
Purpose of the Study:
- To evaluate the performance of the Biocartis Idylla™ MSI assay for detecting MSI in EC.
- To assess the assay's agreement with standard MMR IHC testing.
- To determine the suitability of the Idylla MSI assay for routine clinical diagnostics.
Main Methods:
- The study utilized 35 EC formalin-fixed paraffin-embedded (FFPE) tumor sections (25 dMMR, 10 MSS).
- The Idylla™ MSI assay, a real-time PCR test, was used to detect MSI biomarkers in seven specific genes.
- Macrodissection was performed for samples with ≤20% tumor content; results were compared against MMR IHC.
Main Results:
- The Idylla MSI assay demonstrated 97% overall agreement with MMR IHC (31/32 cases).
- The assay achieved 96% sensitivity and 100% specificity for MSI detection.
- The study highlighted the importance of evaluating the recommended 20% tumor content cut-off for accurate results.
Conclusions:
- The Idylla™ MSI assay is a reliable and automated method for detecting MSI in EC.
- The assay offers advantages such as minimal hands-on time, rapid turnaround, and direct use of FFPE samples.
- This assay provides a valuable tool for MSI testing in EC, aiding in Lynch syndrome screening and immunotherapy selection.
