MMR Panel by IHC

Microsatellite instability (MSI) and/or immunohistochemistry (IHC) testing is performed to analyze colon and other tumor tissue samples to determine if the tumor is microsatellite unstable. MSI testing can detect an abnormal number of microsatellite repeats, which indicates a defective mismatch repair (MMR) gene. A result of microsatellite instability-high (MSI-H) means that a high number of microsatellite repeats were found. IHC testing can detect the presence or absence of the protein products of the MMR genes. A missing protein suggests a mutation in the gene. MSI-H or dMMR solid tumors Many solid tumors can be microsatellite instability-high, including colorectal, endometrial, biliary, gastric, pancreatic, breast and prostate cancer.1 Patients with dMMR or MSI-H tumors may benefit from immune checkpoint inhibitor therapy in first-line and subsequent therapy settings:1,2 Pembrolizumab is indicated for the treatment of adult and pediatric patients with unresectable or metastatic, MSI-H or dMMR: Solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or For the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) Nivolumab, as a single agent, or in combination with ipilimumab, is FDA approved to treat patients with MSI-H or dMMR metastatic CRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin and irinotecan.3 NCCN Guidelines® Recommendations Colorectal Cancer The NCCN Guidelines® recommend universal MMR or MSI testing for all patients with a personal history of colorectal cancer:4 High frequency microsatellite instability is found in 15-20% of all colorectal cancers (CRC); 3% are those associated with Lynch Syndrome. CRC Patients with dMMR or MSI-H tumors may benefit from immune checkpoint inhibitor therapy. Pembrolizumab is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).1 CRC Patients with stage II MSI-H tumors may have a good prognosis and do not benefit from 5-FU adjuvant therapy, and adjuvant therapy should not be given to patients with low-risk stage II MSI-H tumors.4 Endometrial Cancer The NCCN Guidelines® recommend universal MMR or MSI testing for all patients with a personal history of endometrial cancer. MLH-1 loss should be further evaluated for promoter methylation to differentiate sporadic tumors versus germline mutation (Lynch Syndrome).5 Endometrial cancer patients with dMMR or MSI-H tumors may benefit from immune checkpoint inhibitor therapy in the second and third line setting.2

Immunohistochemistry (IHC)

Pembrolizumab package insert. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf Accessed on June, 2020 Le, D.T. et al, PD-1 blockade in tumors with mismatch-repair deficiency, N Engl J Med 2015; 372:2509-20. nivolumab [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2018 The NCCN® Colon Cancer Clinical Practice Guidelines in Oncology (Version 2.2017). ©National Comprehensive Cancer Network, Inc. 2017. The NCCN® Uterine Neoplasms Clinical Practice Guidelines in Oncology (Version 2.2017). ©National Comprehensive Cancer Network, Inc. 2017.