VENTANA® MMR RxDx Panel

US-FDA
VENTANA MMR RxDx panel icon
FDA approved to identify patients eligible for treatment with JEMPERLI® (dostarlimab-gxly), KEYTRUDA® (pembrolizumab), IMFINZI® (durvalumab), or a combination of KEYTRUDA (pembrolizumab) and LENVIMA® (lenvatinib).

The VENTANA MMR RxDx Panel is indicated as an aid in identifying patients eligible for treatment with the following, in accordance with the approved therapeutic product labeling:

  • JEMPERLI (dostarlimab-gxly) or KEYTRUDA (pembrolizumab) for MMR deficient solid tumors, including endometrial carcinoma
  • A combination of KEYTRUDA (pembrolizumab) and LENVIMA (lenvatinib) for MMR proficient endometrial carcinoma
  • IMFINZI (durvalumab) for MMR deficient endometrial carcinoma

It is estimated that up to 4% of all solid tumors are dMMR.1 Cancer continues to be a significant societal challenge as the 2nd leading cause of death in the United States and worldwide.2 In the US, the vast majority of new cases will consist of solid tumors, approximately 16% of which will have been shown to have defects in any of the MMR proteins. Patients with dMMR solid tumors that have progressed on or following prior treatment and have no other options are now eligible for these therapies.3

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What is mismatch repair (MMR)?

DNA mismatch repair is a system for recognizing and repairing errors that can spontaneously occurs during DNA replication. When this mismatch repair mechanism isn’t working properly, it is most commonly attributed to mutations in the MMR proteins, MLH1, PMS2, MSH2, and MSH6.

MMR figure

Take an in-depth look at our VENTANA MMR RxDx Panel:

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    Anatomic pathology provider examining IHC slide

    MMR deficiency serves as a predictive biomarker for new immunotherapeutic options for patients.1

    Multiple studies have demonstrated that MMR deficiency correlate with higher expression of PD-1 or PD-L1, possibly due to increased neoantigen expression associated with tumor mutation burden that results from replication errors.4,5 Thus, MMR proteins may be useful as predictive biomarkers for PD-1 targeted therapy; specifically, a loss of expression of one or more MMR proteins might predict an increased likelihood of response to such therapy. For endometrial carcinoma patients without this MMR deficiency (MMR proficiency, or pMMR) PD-1 inhibitors may retain activity when combined with a TKI.6,7,8

    Intended use

    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) tissue specimens 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 is indicated as an aid in identifying patients eligible for treatment with the therapies listed in Table 1 for the indication and MMR status in accordance with the approved therapeutic product labeling.

    Panel interpretation

    A loss of expression of any of the essential MMR proteins, including MLH1, PMS2, MSH2, or MSH6, in the presence of evaluable internal controls causes MMR deficiency. Presence of staining for all four MMR protein markers in the tumor in the presence of evaluable internal controls indicates that the case is proficient for mismatch repair status. Absence of staining in any one of the MMR protein markers of VENTANA MMR RxDx Panel indicates a case is deficient for mismatch repair status.

    Deficient Case 1: MSH2 and MSH6 Loss Status in gastric adenocarcinoma

    Deficient Case 1: MSH2 and MSH6 Loss Status in gastric adenocarcinoma exhibiting no nuclear staining in tumor cells in the presence of appropriately stained internal controls. MLH1 and PMS2 exhibit Intact Status in this case. Cytoplasmic staining is disregarded for interpretation of status. The acceptable Negative Reagent Controls are mouse NRC (mNRC) and rabbit NRC (rNRC).

    VENTANA Roche mmr rxdx deficient case 1

    Deficient Case 2: MLH1 and PMS2 Loss Status in lung adenocarcinoma

    Deficient Case 2: MLH1 and PMS2 Loss Status in lung adenocarcinoma exhibiting no nuclear staining in tumor cells in the presence of appropriately stained internal controls. MSH2 and MSH6 show Intact Status. Cytoplasmic staining is disregarded for interpretation of status. The acceptable Negative Reagent Controls are mouse NRC (mNRC) and rabbit NRC (rNRC).

    VENTANA Roche mmr rxdx deficient case 3

    Deficient Case 3: MLH1 and PMS2 Loss Status in endometrial adenocarcinoma

    Deficient Case 3: MLH1 and PMS2 Loss Status in endometrial adenocarcinoma exhibiting no nuclear staining in tumor cells in the presence of appropriately stained internal controls. MSH2 and MSH6 exhibit Intact Status. Cytoplasmic staining is disregarded for interpretation of status. The acceptable Negative Reagent Controls are mouse NRC (mNRC) and rabbit NRC (rNRC).

    VENTANA Roche mmr rxdx deficient case 4

    Proficient Case 1: MLH1, PMS2, MSH2 and MSH6 Intact Status in endometrial carcinoma

    Proficient Case 1: MLH1, PMS2, MSH2 and MSH6 Intact Status in endometrial carcinoma exhibiting strong nuclear staining in tumor cells in the presence of appropriately stained internal controls. The acceptable Negative Reagent Controls are mouse NRC (mNRC) and rabbit NRC (rNRC).

    mmr rxdx proficient case 2

    Proficient Case 2: MLH1, PMS2, MSH2 and MSH6 Intact Status in urothelial carcinoma of the urinary bladder

    Proficient Case 2: MLH1, PMS2, MSH2 and MSH6 Intact Status in urothelial carcinoma of the urinary bladder exhibiting strong nuclear staining in tumor cells in the presence of appropriately stained internal controls. The acceptable Negative Reagent Controls are mouse NRC (mNRC) and rabbit NRC (rNRC).

    mmr rxdx proficient case 1

    Proficient Case 3: MLH1, PMS2, MSH2 and MSH6 Intact Status in invasive ductal carcinoma of the breast

    Proficient Case 3: MLH1, PMS2, MSH2 and MSH6 Intact Status in invasive ductal carcinoma of the breast exhibiting strong nuclear staining in tumor cells in the presence of appropriately stained internal controls. The acceptable Negative Reagent Controls are mouse NRC (mNRC) and rabbit NRC (rNRC).

    mmr rxdx proficient case 2

    About the VENTANA MMR IHC Panel

    The VENTANA MMR IHC Panel was launched in 2017 as an aid in the identification of Lynch syndrome in patients diagnosed with colorectal cancer. In addition to the same four MMR proteins listed above (MLH1, MSH2, MSH6 and PMS2), the VENTANA MMR IHC Panel also includes VENTANA BRAF V600E (VE1) Mouse Monoclonal Antibody. The combination of these five antibodies are used clinically to aid in the identification of Lynch syndrome, which is a genetic predisposition for colorectal and other cancers.

    The antibodies in the VENTANA MMR RxDx Panel are the same as those included in the VENTANA MMR IHC Panel, except for VENTANA BRAF V600E (VE1) - same part numbers, same package inserts, but with two separate intended uses. By keeping the part numbers for the antibodies the same, this offers the opportunity for customers to more easily utilize the additional indication.

    References

    1. Le et al., Science 357, 409-413 (2017). 
    2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020:70(1):7-30.
    3. Lorenzi M, Amonkar M, Zhang J, et. al. Epidemiology of Microsatellite Instability High (MSI-H) and Deficient Mismatch Repair(dMMR)in Solid Tumors: A Structured Literature Review. J. Oncology. 2020; (22):1-17.
    4. 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. 
    5. Xiao X, Dong D, He W, et al. Mismatch repair deficiency is associated with MSI phenotype, increased tumor-infiltrating lymphocytes and PD-L1 expression in immune cells in ovarian cancer. Gynecol Oncol. 2018;149(1):146-154. 
    6. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-413. 
    7. Sloan EA, Ring KL, Willis BC, et al. PD-L1 expression in mismatch repair-deficient endometrial carcinomas, including Lynch syndrome-associated and MLH1 promoterhypermethylated tumors. Am J Surg Pathol. 2017;41(3):326-333. 
    8. Dudley JC, Lin MT, Le DT, et al. Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res. 2016;22(4):813-820.1. Lortet-Tieulent J, J Ferlay, F Bray, and A Jemal. (2018) International patterns and trends in endometrial cancer incidence, 1978-2013. J Natl Cancer Inst. 110, 354-361.
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