For patients diagnosed with endometrial cancer, unfamiliar terms like “MMR-deficient” or “p53 abnormal” may appear in their pathology report, leaving them unsure of what these results mean or what questions to ask their doctor. To clarify the meaning of these terms, Monica Avila, MD, MPH, a gynecologic oncologist at Moffitt Cancer Center, and Gulisa Turashvili, MD, PhD, subspecialty director of gynecologic pathology at Mass General Brigham, explained the purpose and findings of biomarker testing.
Biomarker testing examines the genes and proteins in a tumor to help the care team understand how the cancer may behave and which treatments may be most helpful. According to Dr. Avila, tumor testing “has become standard across the United States.” The first tests look for certain proteins that may be missing from the tumor, which can help show whether the cancer may be connected to an inherited condition.
Biomarker Testing Overview
Biomarker testing commonly includes mismatch repair (MMR) proteins, hormone receptors such as estrogen and progesterone, p53, and POLE mutation status. Dr. Turashvili noted that broader genomic profiling may also be performed in some patients. The testing can often be done using tissue already collected during a biopsy or hysterectomy, eliminating the need for another procedure.
The result turnaround time varies depending on the type of test. Simpler tests, such as immunohistochemistry, can take “3-5 days,” while more detailed genomic profiling can take “2-4 weeks or longer,” according to Dr. Turashvili. She recommends asking the care team which tests were ordered and when to expect the results.
Molecular Subtypes Explained
Genomic testing places endometrial cancer into four molecular subtypes: POLE (ultramutated), MMR-deficient, p53-abnormal, and NSMP (no specific molecular profile). Each subtype may behave differently and respond better to different therapies. For example, Dr. Avila described POLE tumors as “the blandest or mildest types of cancers from a molecular standpoint,” and researchers are studying whether some patients with POLE tumors can safely receive less treatment.
MMR-deficient tumors, on the other hand, “respond very well to immunotherapy,” according to Dr. Avila. The p53-abnormal tumors are considered “the most aggressive,” as the p53 protein normally helps stop tumors from growing. NSMP tumors are “the wild card tumors” because they aren’t driven by one recurring mutation.
A 2026 review in the journal Cancers found that about 7% of endometrial cancers are POLE, 28% are MMR-deficient, and 40% are NSMP. Most of the remaining tumors are p53-abnormal. Understanding the molecular subtype can help guide treatment and provide important information about the cancer’s behavior.
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For instance, an MMR-deficient result may indicate that immunotherapy is an option, while a POLE mutation may mean that less treatment is necessary. Dr. Avila noted that clinical trials are exploring what less treatment could safely look like for patients with POLE tumors, which may include skipping chemotherapy, radiation, or both.
The molecular subtype results can also affect cancer staging. Under the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system, POLE tumors may be reclassified to a lower stage, while some p53-abnormal tumors may be reclassified to a higher stage. Patients should ask their care team to review their results and explain how they may affect treatment options.
To find molecular testing results in a pathology report, patients should look for section headings such as Immunohistochemistry, Special Stains, Molecular Pathology, or Molecular Studies. They should also check for separate documents titled Addendum, Supplemental Report, or Genomic Profiling Report, and key terms like MLH1, PMS2, MSH2, MSH6, mismatch repair, MMR-deficient, MSI-high, MSS, POLE, p53, or next-generation sequencing.
Dr. Turashvili explained that MMR-deficient and MSI-high results describe “the same problem from two different angles.” MMR testing uses immunohistochemistry to examine the four proteins under a microscope, while MSI testing uses DNA-based tests to look directly at the microsatellites for signs of instability. The choice between these tests can depend on the laboratory and the specific circumstances of the patient’s case, with Dr. Turashvili noting that guidelines from the College of American Pathologists (CAP) recommend MMR immunohistochemistry over MSI testing when determining eligibility for immunotherapy.
Treatment Options Vary
Treatment options can vary based on the molecular subtype of endometrial cancer. For instance, patients with HER2-positive tumors may receive targeted therapy in addition to chemotherapy.
The FDA has approved several treatments for endometrial cancer, including Jemperli and Keytruda for MMR-deficient or MSI-high tumors. Enhertu is also approved for previously treated HER2-positive solid tumors.
Treatment and Staging
Laboratories use various tests and terminology, so patients may see different terms in their pathology report. Common reference laboratories include FoundationOne, Tempus, Caris, Myriad, and Guardant.
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Lynch Syndrome Risks
Lynch syndrome is an inherited condition that increases the risk of certain cancers.
The National Cancer Institute recommends testing for Lynch syndrome in women diagnosed with endometrial cancer.
A pattern of missing MMR proteins can provide clues about the cause of abnormal results.
If a tumor is missing MLH1 and PMS2, a methylation test is typically ordered.
If methylation is found, Lynch syndrome is usually ruled out.
Germline genetic testing looks for genetic changes present at birth and is usually done with a genetic counselor’s support.
A positive result may affect biological relatives, who may also undergo testing.
