Loong, Lucy, Huntley, Catherine, Pethick, Joanna, McRonald, Fiona, Santaniello, Francesco, Shand, Brian, Tulloch, Oliver, Goel, Shilpi, Lüchtenborg, Margreet, Allen, Sophie, Torr, Bethany, Snape, Katie, George, Angela, Lalloo, Fiona, Norbury, Gail, Eccles, Diana M., Tischkowitz, Marc, Antoniou, Antonis C., Pharoah, Paul, Shaw, Adam, Morris, Eva, Burn, John, Monahan, Kevin, Hardy, Steven and Turnbull, Clare (2024) Lynch syndrome diagnostic testing pathways in endometrial cancers: a nationwide English registry-based study. Journal of Medical Genetics, 61 (12). (doi:10.1136/jmg-2024-110231).
Abstract
Background: for female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS.
Methods: a retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset. For all EC diagnosed in 2019, the proportion tested, median time to test, yield of abnormal results and factors influencing testing pathway initiation were examined.
Results: there was an immunohistochemistry (IHC) or microsatellite instability (MSI) test recorded for 17.8% (1408/7928) of patients diagnosed with EC in 2019. Proportions tested varied by Cancer Alliance and age. There was an MLH1 promoter hypermethylation test recorded for 43.1% (149/346) of patients with MLH1 protein IHC loss or MSI. Of patients with EC eligible from tumour-testing, 25% (26/104) had a germline MMR test recorded. Median time from cancer diagnosis to germline MMR test was 315 days (IQR 222-486).
Conclusion: this analysis highlights the regional variation in recorded testing, patient attrition, delays and missed opportunities to diagnose LS, providing an informative baseline for measuring the impact of the national guidance from the National Institute for Health and Care Excellence on universal reflex LS testing in EC, implemented in 2020.
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