From the Guidelines
All women diagnosed with endometrial cancer should be considered for Lynch syndrome testing, as it can significantly reduce cancer-related mortality through early detection and prevention strategies. This recommendation is based on the most recent and highest quality study, which suggests that universal screening for Lynch syndrome in women with endometrial cancer can identify those at high risk of developing other cancers, such as colorectal cancer, and allow for early intervention 1. The testing typically begins with tumor screening tests such as microsatellite instability (MSI) testing or immunohistochemistry (IHC) for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2).
Some key points to consider when testing for Lynch syndrome include:
- Women diagnosed before age 50, those with a personal or family history of Lynch-associated cancers (colorectal, ovarian, gastric, urinary tract), or those with specific tumor characteristics are at particularly high risk 1.
- Early identification of Lynch syndrome allows for enhanced cancer surveillance, including more frequent colonoscopies starting at an earlier age, consideration of risk-reducing surgeries, and cascade testing of family members who may also carry the mutation 1.
- The importance of early detection remains critical, even in older patients, as it can still have a significant impact on reducing cancer-related mortality 1.
Overall, the benefits of universal screening for Lynch syndrome in women with endometrial cancer outweigh the costs, and it is a crucial step in reducing cancer-related mortality and improving patient outcomes.
From the Research
Screening for Lynch Syndrome in Endometrial Cancer Patients
- Universal tumor testing for defective DNA mismatch repair (MMR) is recommended for all women diagnosed with endometrial cancer to identify those with underlying Lynch syndrome 2.
- Studies have shown that a significant number of Lynch syndrome-associated endometrial carcinomas are missed using clinical, histologic, and locational screening parameters, providing support for universal screening of all newly diagnosed endometrial cancers 3.
- The effectiveness of screening methods, such as MMR protein immunohistochemistry, microsatellite instability (MSI) analysis, and MLH1 methylation testing, has been evaluated in several studies 2, 3, 4, 5, 6.
Test Accuracy and Cost-Effectiveness
- Immunohistochemistry and MSI-based testing strategies have been compared, with no clear difference in accuracy observed between the two methods 5.
- The addition of MLH1 promoter hypermethylation testing to immunohistochemistry may improve specificity 5.
- Economic models have suggested that testing women with endometrial cancer for Lynch syndrome is cost-effective, with immunohistochemistry with MLH1 promoter hypermethylation testing being the most cost-effective strategy 5.
Prevalence of Lynch Syndrome and Double Somatic MMR Gene Pathogenic Variants
- The weighted prevalence of Lynch syndrome germline mutations has been estimated to be around 15-19% in patients with endometrial cancer 2.
- Double somatic MMR gene pathogenic variants have been found to be as common as Lynch syndrome among endometrial cancer patients, highlighting the importance of paired tumor and germline testing for patients with non-methylated dMMR tumors 6.