MMRd stands for mismatch repair deficient.
In the context of medical testing, particularly in cancer diagnostics, MMRd indicates that one or more of the mismatch repair (MMR) proteins are not being identified or are not functioning properly. This deficiency in the mismatch repair system has significant implications for understanding and treating certain cancers.
Understanding Mismatch Repair (MMR)
Mismatch repair (MMR) is a crucial DNA repair mechanism that corrects errors made during DNA replication. These errors often involve mismatched base pairs that were incorrectly incorporated by DNA polymerase. The MMR system acts as a "spellchecker" for our DNA, ensuring genetic stability. The key proteins involved in this process include:
- MLH1
- MSH2
- MSH6
- PMS2
Implications of MMR Deficiency (MMRd)
When the MMR system is deficient (MMRd), these errors are not corrected, leading to an accumulation of mutations, particularly in microsatellite regions. This results in a condition known as microsatellite instability (MSI).
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Microsatellite Instability (MSI): MSI is a hallmark of MMRd. Microsatellites are short, repetitive DNA sequences. In MMRd tumors, these sequences exhibit length variations (instability) compared to normal cells due to the uncorrected errors.
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Cancer Development: MMRd and MSI are frequently observed in certain cancers, including:
- Colorectal cancer (particularly Lynch syndrome-associated colorectal cancers)
- Endometrial cancer
- Gastric cancer
- Other cancers
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Predictive and Prognostic Significance: MMRd status can be used as a predictive biomarker for response to certain immunotherapies, such as immune checkpoint inhibitors. Additionally, MMRd status can have prognostic implications in some cancers.
Testing for MMRd
MMRd is typically assessed through immunohistochemistry (IHC) or microsatellite instability (MSI) testing.
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Immunohistochemistry (IHC): IHC involves staining tissue samples with antibodies that specifically bind to the MMR proteins (MLH1, MSH2, MSH6, PMS2). If one or more of these proteins are not detected, it indicates MMRd.
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Microsatellite Instability (MSI) Testing: MSI testing involves analyzing microsatellite markers in tumor and normal tissue. If a significant proportion of the markers show instability, it indicates MSI and suggests MMRd.
MMRd vs. MMRp
The opposite of MMRd is MMRp, which stands for mismatch repair proficient. This means that the MMR proteins are expressed normally, and the mismatch repair system is functioning as expected.
In summary, MMRd signifies a deficiency in the mismatch repair system, leading to microsatellite instability and increased mutation rates, which can be relevant for cancer diagnosis, prognosis, and treatment decisions.
