First and only MMR IHC assay approved to assess likelihood of response to:
Cancer continues to be a significant societal challenge as the 2nd leading cause of death in the United States and worldwide.1 In the US, approximately 1.9 million new cancer cases were expected to be diagnosed in 2022.1 Of these cases, the vast majority will consist of solid tumors, approximately 14% of which will have been shown to have defects in any of the MMR proteins.
Endometrial carcinoma is the most common gynecological malignant disease, and the fourth most common cancer in North American women.6,7 It is one of the leading causes of cancer -related death in the world.8 EC is frequently noted to have many genetic alterations including MSI.15 MSI-H and dMMR has been reported in 20-40% of endometrial cancers.9,10,11
About DNA Mismatch Repair (MMR)
DNA mismatch repair (MMR) is a conserved molecular mechanism that functions to correct the improper base substitutions that spontaneously occur during DNA replication.2 Defects in the MMR machinery have been attributed to mutations in the MMR proteins, most commonly MLH1, PMS2, MSH2, and MSH6.
The MLH1 and PMS2 proteins normally function together in a heterodimeric complex, as do the MSH2 and MSH6 proteins. When MMR is functioning normally, the MSH6/MSH2 heterodimer binds to mismatched DNA. This binding induces a conformational change that allows the MLH1/PMS2 heterodimer to bind the DNA-bound MSH6/MSH2 complex, resulting in excision repair of the affected DNA.3,4 Mutations or deficiencies in these proteins result in frequent MSI and somatic mutation due to replication error. MMR immunohistochemistry (IHC) testing can be useful in identifying MMR genes likely to contain germline or a somatic alterations.5
Figure 1: MMR proteins and their interactions with DNA. The MSH2-MSH6 complex recognizes mismatches and insertion/deletion loops. The MLH1-PMS2 complex facilitates excision and repair of the mutant bases(s).
A loss of expression of any of the essential MMR proteins, including MLH1, PMS2, MSH2, or MSH6, in the presence of evaluable internal controls identifies MMR deficiency.
Figure 1: VENTANA anti-MLH1 (M1) Mouse Monoclonal Primary Antibody staining with Intact (left) or Loss (right) of expression in the presence of evaluable internal controls in endometrial carcinoma tissue.
Figure 3: VENTANA anti-MSH2 (GS19-1129) Mouse Monoclonal Primary Antibody staining with Intact (left) or Loss (right) of expression in the presence of evaluable internal controls in endometrial carcinoma tissue.
Figure 2: VENTANA anti-MSH6 (SP93) Rabbit Monoclonal Primary Antibody staining with Intact (left) or Loss (right) of expression in the presence of evaluable internal controls in endometrial carcinoma tissue.
Figure 4: VENTANA anti-PMS2 (A16-4) Rabbit Monoclonal Primary Antibody staining with Intact (left) or Loss (right) of expression in the presence of evaluable internal controls in endometrial carcinoma tissue.
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020:70(1):7-30.
2. Hsieh P, Yamane K. DNA mismatch repair: Molecular mechanism, cancer, and ageing. Mech Ageing Dev. 2008;129(7-8):391-407.
3. Buza N, Ziai J, Hui P. Mismatch repair deficiency testing in clinical practice. Expert Rev Mol Diagn. 2016;16(5):591-604.
4. Silva FCC, Torrezan GT, Ferreira JRO, et al. Germline mutations in MLH1 leading to isolated loss of PMS2 expression in Lynch syndrome: implications for diagnostics in the clinic. Am J Surg Pathol. 2017;41(6):861-864.
5. Cunningham JM, Tester DJ, Thibodeau SN. Mutation detection in colorectal cancers: direct sequencing of DNA mismatch repair genes. Methods Mol Med. 2001;50:87-98.
6. Yamashita H, Nakayama K, Ishikawa M, et al. Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer. Oncotarget. 2017:9(5):5652-5664.
7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019:69(1):7-34.
8. Pisani P, Bray F, Parkin DM. Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer. 2002:97(1):72-81.
9. Kato M, Takano M, Miyamoto M, et al. DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers. J Gynecol Oncol. 2015:26(1):40-45.
10. Matthews KS, Estes JM, Conner MG, et al. Lynch syndrome in women less than 50 years of age with endometrial cancer. Obstet Gynecol. 2008:111(5):1161-6.
11. Kim SR, Pina A, Albert A, et al. Does MMR status in endometrial cancer influence response to adjuvant therapy? Gynecol Oncol. 2018:151(1):76-81
VENTANA MMR RxDx Panel is a qualitative immunohistochemistry test intended for use in the assessment of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) in formalin-fixed, paraffin-embedded (FFPE) tissues by light microscopy. The OptiView DAB IHC Detection Kit is used for MLH1, MSH2 and MSH6, and the OptiView DAB IHC Detection Kit with the OptiView Amplification Kit is used for PMS2 on a VENTANA BenchMark ULTRA instrument.
VENTANA MMR RxDx Panel includes VENTANA anti-MLH1 (M1) Mouse Monoclonal Primary Antibody, VENTANA anti-PMS2 (A16-4) Mouse Monoclonal Primary Antibody, VENTANA anti-MSH2 (G219-1129) Mouse Monoclonal Primary Antibody and VENTANA anti-MSH6 (SP93) Rabbit Monoclonal Primary Antibody.
VENTANA MMR RxDx Panel is indicated as an aid in identifying patients eligible for treatment with JEMPERLI (dostarlimab-gxly) therapy in Deficient MMR (dMMR) Solid Tumors, including Endometrial Carcinoma (EC), or KEYTRUDA (pembrolizumab) Deficient MMR (dMMR) Solid Tumors, including Endometrial Carcinoma (EC).
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. For more information visit https://www.keytruda.com/
|VENTANA anti-MLH1 (M1) Mouse Monoclonal Primary Antibody||790-5091||07862237001||50 tests|
|VENTANA anti-PMS2 (A16-4) Mouse Monoclonal Primary Antibody||790-5094||07862261001||50 tests|
|VENTANA anti-MSH2 (G219-1129) Mouse Monoclonal Primary Antibody||790-5093||07862253001||50 tests|
|VENTANA anti-MSH6 (SP93) Rabbit Monoclonal Primary Antibody||790-5092||07862245001||50 tests|
|OptiView DAB IHC Detection Kit||760-700||06396500001||250 tests|
|OptiView Amplification Kit*||860-099||06718663001||250 tests|