Key Insights

• Understand how this test reveals your tumor’s DNA repair status to identify microsatellite instability and mismatch repair deficiency linked to endometrial cancer.
• Identify whether key mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) are functioning, and whether the tumor is MSI-high—findings that help explain tumor behavior and potential hereditary risk.
• Learn how genetic and epigenetic influences, such as inherited Lynch syndrome or MLH1 promoter methylation, may be shaping your results and future risk profile.
• Use insights to guide treatment discussions with your clinician, including eligibility for immunotherapy and the need for genetic counseling when Lynch syndrome is suspected.
• Track whether results are consistent across biopsies or at recurrence to understand stability of the tumor’s biology and response patterns over time.
• When appropriate, integrate this test with related panels—such as POLE mutation status, p53 status, tumor mutation burden, hormone receptor markers, and standard staging—to build a complete picture that informs prognosis and care planning.

What Is an MSI/dMMR Test?

An MSI/dMMR test evaluates whether an endometrial tumor has impaired DNA mismatch repair (dMMR) or microsatellite instability (MSI), both of which signal a high mutation rate within cancer cells. The test is performed on tumor tissue from an endometrial biopsy or surgical specimen. Pathologists typically use immunohistochemistry (IHC) to check if the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 are present in tumor cell nuclei. Loss of one or more proteins suggests dMMR. In parallel or as confirmation, PCR or next-generation sequencing (NGS) measures MSI by examining short, repetitive DNA regions that become unstable when repair is faulty. Results are reported as dMMR versus proficient MMR, and MSI-high (MSI-H), MSI-low, or microsatellite stable (MSS), compared to validated reference criteria.

Why it matters: mismatch repair is a core cellular quality-control system. When it falters, mutations accumulate faster, shaping how a tumor grows, how the immune system recognizes it, and how it may respond to treatment. In endometrial cancer, dMMR/MSI-H is common (roughly one-quarter to one-third of cases) and can uncover Lynch syndrome in a subset of patients. Testing gives objective, guideline-aligned data that informs diagnosis, hereditary risk assessment, and therapeutic options—especially the potential benefit from immune checkpoint inhibitors in advanced or recurrent disease.

Why Is It Important to Test Your MSI/dMMR?

MSI and mismatch repair status connect directly to how a tumor maintains its genome. When the repair crew is off duty, errors stack up, creating a mutation-rich cancer that may generate neoantigens—novel signals the immune system can spot. In endometrial cancer, this biology explains several clinical realities: dMMR/MSI-H tumors are a defined molecular subgroup, can indicate an inherited mismatch repair gene variant (Lynch syndrome), and often show different responses to therapy than tumors with intact repair. Testing is especially relevant at initial diagnosis, at recurrence, and when a patient is younger than expected for endometrial cancer or has a family history suggestive of Lynch syndrome. As a relatable analogy, think of this as a quality-control audit for the tumor: are the proofreading tools working, or is the spell-checker broken and letting typos pile up?

Stepping back, MSI/dMMR testing turns a single pathology report into an actionable roadmap. It helps detect hereditary cancer risk, informs prognosis alongside stage and grade, and guides modern treatments like immunotherapy in advanced settings. It also standardizes follow-up decisions—for example, whether to reflex to MLH1 promoter methylation testing when MLH1/PMS2 loss is seen to distinguish sporadic epigenetic silencing from inherited risk. The goal isn’t to “pass” or “fail.” It’s to understand where your tumor sits on the molecular spectrum and use that knowledge to shape safer, smarter long-term care.

What Insights Will I Get From a MSI/dMMR Test?

Your report typically displays results in two complementary ways. First, IHC shows whether the four mismatch repair proteins are present. If one or more are missing in tumor cells (with intact staining in surrounding normal cells as an internal control), the tumor is labeled dMMR. Second, MSI testing classifies the tumor as MSI-high, MSI-low, or microsatellite stable by comparing specific DNA regions to reference standards. “Normal” in this context means what is typical for non-defective repair; “optimal” means a profile associated with clearer therapeutic and hereditary decision-making. Context matters: a dMMR/MSI-H result carries different implications in a newly diagnosed, early-stage tumor than in a recurrent, treatment-resistant one.

Balanced or proficient results suggest intact repair and a mutation rate more in line with typical tumors. That can point to different treatment pathways and a lower likelihood of Lynch syndrome. Variability happens because biology is nuanced—fixation quality of tissue affects IHC, tumor heterogeneity can create patchy staining, and rare tumors exhibit discordance between IHC and MSI. Laboratories mitigate this with validated controls and, when indicated, reflex testing.

Higher-instability or protein-loss findings (MSI-H or dMMR) may indicate a tumor more visible to the immune system and, in advanced settings, potential eligibility for immune checkpoint inhibitor therapy. They also trigger consideration of germline evaluation for Lynch syndrome, particularly when MLH1 loss is not due to promoter methylation. Abnormal results do not equal a specific prognosis by themselves. They are interpreted alongside tumor stage, grade, depth of invasion, lymphovascular space involvement, hormone receptor status, and other molecular markers (such as POLE and p53) to refine risk and options.

The real power here is pattern recognition over time. While MSI/dMMR status is usually stable, retesting at recurrence can confirm whether biology has shifted and whether targeted options remain relevant. When combined with personal history and related biomarkers, this test supports earlier detection of hereditary risk, more precise treatment selection in advanced disease, and a clearer understanding of your path forward—without guesswork.