Rates of dMMR status in endometrial hyperplasia in comparison to MMR related Lynch Syndrome of endometrial cancer: a pilot study

Background: Lynch syndrome is the most common cause of hereditary endometrial cancer, and is associated with defective DNA mismatch repair. The purpose of the study was to identify the rate of mismatch repair deficiency in women with endometrial hyperplasia compared with the rate in endometrial cancer. Methods: A retrospective cohort pilot study was conducted to identify the frequency of mismatch repair deficiency in endometrial hyperplasia specimens, and compare to the known rate in endometrial cancer. A keyword search of the medical record at a single institution was performed to identify 1300 endometrial tissue blocks either from biopsy, curettage or hysterectomy. After exclusion, cohort of 91 women with endometrial hyperplasia were included for analysis. Patient characteristics for both those with normal and abnormal mismatch repair (MMR) results were analyzed using the Mann-Whitney U test and Fisher exact test. Immunohistochemical staining was performed to test for mismatch repair deficiency. Results: Among the 91 women with known endometrial hyperplasia specimens who met inclusion criteria, 4 specimens exhibited mismatch repair deficiency. The observed rate of mismatch repair deficiency in hyperplasia (4.4%), was found to be significantly less than that of mismatch repair deficiency seen in endometrial cancer (25%, p < 0.0001). Conclusions: Based on the data, deficient mismatch repair (dMMR) is not identified at a similar rate in endometrial hyperplasia compared to endometrial cancer. Currently there is no rationale to recommend immunohistochemical staining for mismatch repair deficiency on hyperplasia specimens, and further investigation is recommended to advance screening guidelines for Lynch syndrome. Clnical Trial Registration: NCT05257057.

Mismatch repair deficiency; dMMR; Lynch Syndrome; Hereditary endometrial cancer

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