Identification of Lynch syndrome among people newly diagnosed with endometrial cancer: a prospective audit

Since 2020, the UK National Institute for Health and Care Excellence (NICE) recommends screening for Lynch syndrome in all people newly diagnosed with endometrial cancer. Screening involves tumour testing for loss of the mismatch repair (MMR) proteins using immunohistochemistry (IHC), MLH1 methylation testing and germline sequencing for Lynch syndrome according to a diagnostic algorithm. Here we review adherence to NICE guidance at a gynaecological cancer centre in North-West England.

We conducted a prospective audit of Lynch syndrome screening for consecutive patients newly diagnosed with endometrial cancer discussed at the gynaecological oncology multidisciplinary (MDT) meeting. We recorded adherence with the NICE recommended diagnostic algorithm, testing turnaround times and the impact of gynaecology-led genetic testing (mainstreaming) on diagnostic intervals.

Between November 2021 and November 2023, 421 new endometrial cancer patients were discussed at MDT. Overall, 96.9% (408/421) underwent IHC and 26.0% (106/408) were MMR deficient, mostly due to MLH1 hypermethylation (17.4%, 71/408). In total, 7.1% (29/408) had MMR deficiency not due to MLH1 hypermethylation (25/408 had MSH2/MSH6/PMS2 loss and 4/408 were non-hypermethylated) that required germline testing for Lynch syndrome, and 3.2% (13/408) had Lynch syndrome. Only 19/27 (70.4%) with positive tumour triage underwent Lynch syndrome testing (four declined and four died before testing). The median time from tumour MMR IHC results to germline test result was 121 days (IQR 103, 133) with gynaecology-led testing compared with 278 days (IQR 183, 476) with testing organised by clinical genetics.

The prevalence of Lynch syndrome in our unselected endometrial cancer population was 3.2% but not everyone at risk was tested. Some declined germline Lynch syndrome testing due to a lack of at-risk family members and delay getting their genetic appointment. A significant minority died before they could be offered or receive Lynch syndrome testing. We recommend gynaecology-led germline testing and referral to clinical genetics only patients with confirmed Lynch syndrome. This approach would ease the burden of an already overstretched genetics service while promptly identifying Lynch syndrome in high-risk patients. This in turn enables timely colorectal cancer surveillance and cascade testing of at-risk family members.