Mismatch Repair by Immunohistochemistry & Microsatellite Instability by PCR

Immunotherapy available for tumors identified as dMMR or MSI-H

Patients with unresectable or metastatic solid tumors identified as mismatch repair deficient (dMMR by IHC) or microsatellite instability-high (MSI-H by PCR) who have progressed following other treatments are now eligible for Keytruda® (pembrolizumab) immunotherapy. A recent FDA accelerated approval based on these biomarkers permits the use of Keytruda®  immunotherapy in qualified patients, regardless of solid tumor site.

MMR (Mismatch Repair Proteins) by IHC (Immunohistochemistry)
This IHC assay is used to identify patients who are deficient in MMR proteins: hMLH-1, hMSH-2, hMSH-6, or PMS2. Patients who show loss of one or more of the four DNA mismatch repair proteins (complete absence of nuclear immunoreactivity) should be further evaluated for Lynch Syndrome. Initial screening for Lynch Syndrome in all patients with colorectal carcinoma is recommended by the Evaluation of Genomic Applications in Practice & Prevention (EGAPP™) Working Group.

MSI (Microsatellite Instability) by PCR (Polymerase Chain Reaction)
This PCR assay is used to identify patients who have defective mismatch repair systems characterized by instability in highly repetitive areas of genomic DNA. Five designated markers BAT-25, BAT-26, NR-21, NR-24, and MONO-27 are used to evaluate microsatellite lengths in both normal and tumor tissue samples. Tumor tissue demonstrating a change in microsatellite length is considered unstable. In colorectal carcinoma patients, microsatellite instability (MSI) analysis can be used to identify patients who are less likely to have recurrent disease. 2  Patients with hereditary non-polyposis colorectal carcinoma (HNPCC aka Lynch Syndrome) are more likely to develop tumors with microsatellite instability.

References

1. Vasen HF, Blanco I, Aktan-Collan K, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): Recommendations by a group of European experts. Gut 2013;62:812-23.
2. Sinicrope FA, Foster NR, Sargent DJ, et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst. 2011;103:863-875.