Predictive IHC assay
The VENTANA MMR RxDx Panel is the first and only immunohistochemistry-based assay approved to identify endometrial carcinoma patients eligible for treatment with JEMPERLI (dostarlimab). Endometrial cancer (EC) is the most common gynaecological malignancy in the U.S. and the fourth most common cancer in women in North America.1,2 There are limited treatment options for women whose disease progresses on or after first-line therapy.3
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 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 base(s).
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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.1,9 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.10,11,12
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.
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 (G219-1129) 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.
References
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) endometrial carcinoma tissue by light microscopy. The OptiView DAB IHC Detection Kit is used for MSH6, MSH2 and MLH1, 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 therapies listed in Table 1 for the respective indications and status in accordance with the approved therapeutic product labeling.
| Indication for use | Therapy |
Status |
|---|---|---|
Endometrial Carcinoma (EC) |
JEMPERLI (dostarlimab) | Deficient MMR (dMMR) |
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