Universal screening for Lynch syndrome in endometrial cancer results in increased acceptance of genetic counseling and testing

Abstract

Objectives: To evaluate the effect of a universal screening protocol for all newly diagnosed endometrial cancers for Lynch syndrome (LS) using immunohistochemistry staining (IHC) for mismatch repair (MMR) enzyme expression on subsequent genetic counseling and genetic testing referral and acceptance rates. Methods: We performed a retrospective cohort study of all womenwho underwent a hysterectomy for endometrial cancer at Barnes Jewish Hospital in St. Louis, MO, between January 1, 2011 and December 31, 2013, (n= 637). A universal screening protocol was initiated on December 17, 2012, and used IHC for MMR enzymes MLH1, MSH2, MSH6, and PMS2. Caseswith absentMLH1 stainingwere reflexed toMLH1 promoter methylation testing. The first cohort (Pre Em-USP) consisted of women who presented prior to initiation of the screening protocol and were selectively screened (n= 395). In the second cohort (Em-USP), women presented after initiation of this protocol and were all screened for LS (n= 242). Genetic counseling and genetic testing referrals in both cohortswere based on risk factors (family or personal history) and/or IHC results. Categorical variables were compared using the Fisher's exact tests and continuous variables were compared using the Kruskal–Wallis test. Results: Overall, a greater proportion of individuals in the Em-USP cohort underwent genetic testing than in Pre Em-USP (9.1% vs. 4.8%, P b 0.05). Of the individuals with an IHC screening result suggestive of LS, those in the Em-USP cohort were significantly more likely to accept genetic counseling compared to those in the Pre-Em-USP cohort (95% vs. 64%, P= 0.02). Within the Em-USP cohort specifically, patients referred for genetic counseling due to a concerning IHC screening result compared with those who had a normal MMR enzyme staining pattern and were referred based on other risk factors had a higher counseling acceptance rate (95% vs. 61%, P=0.03) and underwent genetic testing more readily (76% vs. 30%, P b 0.001). Conclusions: Implementation of a universal screening protocol utilizing IHC for LS in endometrial cancer leads to higher acceptance of genetic counseling and higher rates of genetic testing compared to referral based on family or personal history alone.