Frequency of endometrial cancer precursors associated with Lynch Syndrome

Description

This is an observational Cohort study. Tissue specimens obtained that have been labeled with the diagnosis of endometrial hyperplasia will be identified and their chart reviewed for demographic date of age, race, BMI, and co-morbidities. The specimen will then be tested via IHC for MLH1, PMS2, MSH2, or MSH 6 genes to determine the presence of microsatellite instability indicative of Lynch Syndrome. The numbers will then be statistically analyzed and compared to that of the incidence of Lynch syndrome associated with endometrial cancers to see if the incidence is comparable

Steps to reproduce

Sample size determination was made based on a desired power of 80% and alpha = 0.05. A calculated 1782 cases were required to exclude a difference between the groups, i.e. present of dMMR in hyperplasia specimens was equivalent to that of endometrial cancer cases (25%). Given the resources available, a pilot study of approximately 5% of this population, around 89 samples, was sought. Informed consent was obtained via telephone. Participants who met criteria were given the option of a follow up phone call with their results. A copy of the consent form was sent to all participants. No compensation was provided. Chart review was performed for demographic data including age, BMI, race, ethnicity, and personal or family history of endometrial or colon cancer. IHC testing for MLH1, PMS2, MSH2, or MSH 6 was performed and analyzed by a single pathologist. Equivocal results were reviewed with a second pathologist. Women who desired their results were notified of them via phone call. If testing revealed dMMR, those women were counseled by a Gynecologic Oncology fellow and recommended for genetic counseling and testing. Referrals to a licensed genetic counselor for Oncology at the WellSpan institution were placed if the patients were amenable. Patient characteristics for both normal and abnormal MMR results were analyzed using the Mann-Whitney U test (for continuous variables) and Fisher exact test (for categorical variables). The rate of dMMR was computed in this patient population. A z-test of proportion with a significance of p <0.0001 compared it to the known incidence of dMMR in endometrial cancer from the literature

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