Micro-Satellite Instability (MSI)-High Cancers: How and When to Test your Patients
MSI-HIgh cancers are characterized by one or more deleted mismatch repair (d-MMR) proteins MLH1, MSH2, MSH6, and PMS2. Germline (inherited) or somatic (tumor-specific) DNA changes result in loss of these proteins, and either the tumor DNA or tumor cells can be tested to identify MSI-High cancers.
Why is it important to identify MSI-High Tumors?
Commercially available testing for MLH1 and MSH2 was introduced in the 1990s as a screening method for patients with germline (Lynch Syndrome) MSI-High/d-MMR colorectal and endometrial cancers. Initially screening was performed to identify the ~2-4% of colon and endometrial cancers representing patients with early onset Lynch syndrome tumors. More recently it has been noted that characterization of a tumor as MSI-High/d-MMR not only helps identify patients who may have an inherited cancer syndrome but can also be used as a prognostic and predictive biomarker for treatment planning.
How does testing for MSI-HIgh/d-MMR tumors help with Treatment Planning?
Approximately 15% of colorectal cancers are MSI-High/d-MMR. Evidence has shown these tumors to have a more favorable stage-adjusted prognosis than MMR-expressing tumors regardless of whether the loss of mismatch repair proteins is germline or somatic. MSI-high/d-MMR tumors may not benefit from adjuvant 5-FU therapy but recent clinical trial evidence has demonstrated that some MSI-High/d-MMR tumors respond favorably to immunotherapy. Therefore, testing across advanced tumors (including colorectal and endometrial) for the MSI-high and/or d-MMR biomarkers could identify patients predicted to respond to PD-1 blocker immunotherapy.
Which test should be ordered? MSI-High, d-MMR, or both?
- Current NCCN Clinical Practice Guidelines recommend universal MMR or MSI testing for colorectal and endometrial cancers. d-MMR testing is performed by immunohistochemistry (IHC) at the time of diagnosis by Precision Pathology Services for colorectal and endometrial cancers.
- d-MMR testing can also be performed by Precision Pathology across advanced cancers including biliary, esophageal, gastric, pancreatic, small bowel, breast, bladder, renal cell, prostate, retroperotineal, lung, sarcoma and thyroid. If MMR results show MMR deletion, reflex MSI testing is performed to confirm the MSI-High genotype at the DNA level.
- The FDA has approved immunotherapy for patients with MSI-High/d-MMR tumors.
Precision Pathology Services can support all of your MSI/MMR testing needs. Please contact us for more information.
For more information about our Precision Medicine Genomic Pathology, please contact Precision Pathology Services at 210-646-0890, or by email at firstname.lastname@example.org
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