Targeted Screening With Combined Age- and Morphology-Based Criteria Enriches Detection of Lynch Syndrome in Endometrial Cancer

Endometrial cancer is associated with Lynch syndrome in 2% to 6% of cases. Adequate screening may prevent of a second cancer and incident cancers in family members via risk-reducing strategies. The goal of the study was to evaluate the detection rate of Lynch syndrome via a targeted screening approach. In 2009, we incorporated targeted Lynch syndrome screening via immunohistochemistry for MLH1, PMS2, MSH2, and MSH6, followed by MLH1 promoter hypermethylation, in select cases of endometrial carcinoma. Criteria for patient selection included (1) all patients <50 years; (2) patients of any age with tumors showing features of microsatellite instability (lower uterine segment-centered tumors, hard to classify carcinomas, increased peritumoral or tumor infiltrating lymphocytes and cases with synchronous ovarian carcinomas); (3) clinician's request based on family or personal history; and (4) ad hoc retrospective testing based on the established criteria on patients discovered on follow-up visits. By using a targeted screening approach in a 4.5-year period, approximately 2.1% of endometrial cancers (7 of 328) were potentially associated with Lynch syndrome. Therefore, targeted screening with combined age and morphology based criteria enriches detection of Lynch syndrome in endometrial cancer. However, the detection rate is lower than the rates from published series that offer universal screening.