Abstract IA004: Universal tumor screening for Lynch syndrome versus germline multi-gene panel testing for all endometrial cancer patients
Authors: Hampel Heather 
Published: March 2024

Introduction: Implementation of universal tumor screening for Lynch syndrome has been adopted more slowly for endometrial cancer patients than colorectal cancer patients yet the data is very similar. Recent guidelines have suggested doing both universal tumor screening and considering multi-gene panel testing for all colorectal cancer patients and so the data in endometrial cancer patients was reviewed to determine if the same recommendation could be made for endometrial cancer. Methods: Review of the literature found 4 large studies of universal tumor screening for Lynch syndrome among and 6 large studies of universal multi-gene panel testing among large cohorts of endometrial cancer patients. Results were reviewed and a meta-analysis performed. Results: Four large studies have looked at universal tumor screening among all endometrial cancer patients. They found that 23-26.7% of endometrial cancers are MSI-high or dMMR. The majority of these dMMR endometrial cancers are caused by MLH1 promoter hypermethylation which is present in 14-20.2% of all EC cases (60.3-75.8% of dMMR cases). Lynch syndrome was ultimately diagnosed in 2.5-3.3% of all endometrial cancer patients. The mutation distribution among Lynch syndrome patient diagnosed through universal tumor screening was 53.1% MSH6, 24.5% MSH2, 12.2% MLH1, and 10.2% PMS2. IHC was better at identifying Lynch syndrome cases than MSI among endometrial cancers (mainly due to MSH6 tumors not always being MSI-high). Multi-gene panel testing (MGPT) for all endometrial cancer patients has been reported in 6 studies of endometrial cancer patients (3 high risk and 3 unselected). MGPT studies found that 10 – 14% of unselected and 9 - 15% of selected endometrial cancer patients have a pathogenic variant in a cancer susceptibility gene. Patients diagnosed under age 50 were not significantly more likely to test positive. In the three selected cohorts, the prevalence of Lynch syndrome was 8.1% (575/7095). In the three unselected cohorts, the prevalence of Lynch syndrome was 2.7% (73/2742). Conclusions: Tumor screening with MSI or MMR IHC for all endometrial cancers will only identify Lynch syndrome (as intended). It will miss patiesporadicny other hereditary cancer syndrome and some patients with Lynch syndrome who have a sporadic endometrial cancer. However, it is now necessary for treatment purposes (Immune Checkpoint Blockade therapy). Universal germline MGPT testing for all endometrial cancers will identify some Lynch syndrome cases who have normal tumor screening and will identify many non-Lynch syndrome cases that would be completely missed by tumor screening.

Citation Format: Heather Hampel. Universal tumor screening for Lynch syndrome versus germline multi-gene panel testing for all endometrial cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA004.