A Microsatellite Instability (MSI) Series

Screening cancer patients for microsatellite instability (MSI) can provide pathologists, oncologists, and patients with information that characterizes tumors to help guide care and make more informed decisions.  With the growing demand for MSI testing and recognition of its value as a biomarker, the need for a reliable and cost-effective MSI test has increased in recent years. In this presentation, Ms. Oostdik will discuss the new OncoMate™ MSI Dx Analysis System, a FDA-cleared PCR-based MSI kit. The system uses the most sensitive panel of markers for MSI status detection, as included in multiple clinical guidelines. Topics in this presentation will include assay design, intended use, and clinical performance of OncoMate™ MSI Dx. The automated analysis software included in the system will also be discussed.

Learning objectives

• Present the relationship between mismatch repair deficiency and microsatellite instability
• Describe microsatellite instability detection using PCR followed by capillary electrophoresis (CE) analysis
• Describe the use of microsatellite instability status for Lynch Syndrome screening in colorectal cancer (CRC)
• Summarize the performance of the OncoMate™ MSI Dx Analysis System as an aid to identify colorectal cancer (CRC) patients who may benefit from further testing to screen for Lynch syndrome, the most common form of hereditary CRC

Dr. Emily Teslow will discuss MSI testing gold standards and compare the different methods that are currently being used for microsatellite instability (MSI) testing for mismatch repair deficient (dMMR) tumors. Then she will discuss the clinical relevance of the MSI-H biomarker focusing on the pathological and epidemiological characteristics of MSI-H/dMMR tumors, and the role of MSI testing in Lynch syndrome screening, colorectal cancer patient prognosis, and immunotherapy treatment.

Learning objectives

• Compare techniques used to measure microsatellite instability to current gold-standard methods
• Discuss the clinical utility of the MSI biomarker for Lynch syndrome screening and immunotherapy treatment
• Review the most current clinical practice guidelines for MSI testing

Microsatellite instability, a hallmark of mismatch repair-deficient cancers, is typically associated with good response to immunotherapy. We sought to evaluate the merit of using liquid biopsies to detect microsatellite instability in subjects with stage IV colorectal adenocarcinoma.  DNA extracted from ccfDNA and buffy coats was used as source of tumor DNA and germline DNA respectively.  Aberrant microsatellite allele sizes were readily detectable in 7 of 8 cases where baseline or second treatment cycles liquid biopsy samples were available from subjects with mismatch repair-deficient cancers. The only sample that tested negative was from a subject whose primary tumor showed MSI heterogeneity and was unresponsive to immunotherapy.  MSI-H status of longitudinal liquid biopsy samples was found to correlate with response to immunotherapy.  This limited study suggests testing for microsatellite instability in liquid biopsies from subjects with advanced colorectal cancers may help in predicting response to immunotherapy.

Dr. Samantha Lewis will discuss the value of MSI as a biomarker and techniques to measure microsatellite instability. She will then describe the development of a new PCR assay to detect MSI in solid tumors utilizing a new 8-marker panel that includes both gold standard markers and novel long mononucleotide repeats for a research-based approach to maximize sensitivity. Dr. Lewis will demonstrate the utility of this novel panel by showcasing studies using difficult and degraded samples (ccfDNA and FFPE).

Learning Objectives:

• Demonstrate how mismatch repair deficiency causes microsatellite instability
• Recognize techniques to measure microsatellite instability
• Discuss why long mononucleotide markers may offer a different perspective on MSI

Dr. Nguyen will discuss the disparities in colorectal cancer outcomes and how precision medicine has the potential to exacerbate health disparities due to differences in access and implementation.

Learning Objectives:

• Identify disparities in colorectal cancer outcomes.
• Describe the role of MSI testing and implementation in colorectal cancer outcomes.
• Formulate strategies on how to mitigate disparities in MSI testing and implementation in colorectal cancer.

Dr. Blobe will be discussing the use of a universal MSI testing approach to identify candidates for immunotherapeutic treatment of Colorectal and other GI Cancers, including Biliary Tract, Esophageal, Anal, and Gastric Cancers. 

Ms. Hampel will be discussing the growing importance and implications of universal MSI/dMMR screening for Lynch Syndrome-associated cancers to aid in identifying patients and their family members who may be affected. 

Learning Objectives: 

•    State the number of individuals in the U.S. with Lynch Syndrome 
•    Describe the importance of universal screening for identifying individuals with Lynch Syndrome
 

Dr. Eshleman will be discussing how MSI provides a functional readout of mismatch repair status, the implications of mismatch repair deficiency in cancer cells, and how elevated mutation rate associated with MSI-H tumor cells drive the production of neoantigens thought to contribute to immunotherapeutic response.
 

Learning Objectives: 

•    Recall implications of mismatch repair deficiency in solid tumors 
•    Define Key advantages of Long Mononucleotide Repeats (LMRs) in detecting microsatellite instability
 

Dr. Bacher will be discussing the history and evolution of MSI, the differences between popular testing methods, and what the future holds for this powerful biomarker. 

Learning Objectives: 

•    Explain what a microsatellite is, how errors in microsatellites are repaired and indicate how MSI testing is done
•    Compare and contrast the characteristics of laboratory assays used to test for microsatellite instability in solid tumors