Universal testing in endometrial cancer in Sweden

Area of Science:

• Oncology
• Genetics
• Cancer Screening

Background:

• Endometrial cancer (EC) is linked to Lynch Syndrome (LS), a hereditary cancer predisposition.
• Effective screening strategies are crucial for identifying LS cases to enable timely intervention and genetic counseling.
• Current clinical criteria for LS screening may not be sufficiently sensitive for all EC patients.

Purpose of the Study:

• To evaluate the effectiveness of a universal screening strategy for Lynch Syndrome in endometrial cancer cases.
• To compare universal screening with established clinical criteria (Amsterdam II and Bethesda) for LS detection.
• To assess the utility of immunohistochemistry (IHC) for DNA mismatch repair (MMR) proteins in LS prescreening.

Main Methods:

• Immunohistochemistry (IHC) was performed on 221 endometrial cancer cases using antibodies for MLH1, PMS2, MSH2, and MSH6.
• Cases with MMR protein loss (54/221) were selected for further germline mutation screening of MMR genes.
• Comparison of LS detection rates between universal testing, Amsterdam II criteria, and Bethesda criteria.

Main Results:

• Universal screening identified five (2.3%) LS cases, outperforming Amsterdam II and Bethesda criteria, which each detected two (0.9%) cases.
• Combining universal testing with family history criteria also identified five (2.3%) LS patients.
• MMR protein loss was observed in 54 cases, leading to mutation screening in 52.

Conclusions:

• A universal screening strategy using IHC for MMR proteins on all new EC cases diagnosed before age 70 is proposed.
• Mutation screening should prioritize tumors with loss of MSH2 and/or MSH6, or isolated PMS2 loss.
• Consideration for germline mutation screening of all LS genes is recommended for cases meeting Amsterdam II criteria, irrespective of IHC results.