Equality in lynch syndrome screening: why should we hold patients with endometrial cancer to a different standard?

TO THE EDITOR: In their recently published study, Buchanan et al 1 proposed a population screening strategy for the identification of Lynch syndrome in patients with endometrial cancer. In their algorithm, they showed a cost savings benefit with the addition of MLH1 promoter methylation for tumors demonstrating a lack of MLH1/ PMS2 expression. We agree that methylation testing is cost-effective and a necessary step in triaging patients for genetic counseling and genetic testing. However, the authors also determined that screening for women diagnosed before age 60 years optimizes identification of Lynch syndrome. We would like to comment on the pitfalls of using age as a screening criterion in the clinical setting. In this study cohort, only three of 22 women (14%) with pathogenic mismatch repair mutations were older than age 60 years at the timeofdiagnosis. 1 Thisproportionissignificantlylowerthaninother population-based studies. Hampel et al 2,3 found five of 13 women (38%) with Lynch syndrome were diagnosed after age 60 years. In a studybyLeenenetal, 4 threeofsevenwomenwithgermlinemutations (43%) were older than age 60 years. The inherent bias in the present study has likely skewed thefinal cost per carrier in this population. As we have shown, the clinical practice of implementing tumor screeningforLynchsyndromediffersfromresearchpractices. 5 Inour 3 years of screening on the basis of age and molecular characteristics, 27 eligible patients were overlooked by pathologists for screening. Using a universal screening approach, no patients were missed. Eliminatingastepfromthepathologists’workflowtodetermineifapatient meetsscreeningcriteriacutsdownonthechanceforerrorandstreamlines processes. Wealsoraisethisquestion:whyshouldweplacestringentcriteria on screening for endometrial cancers when universal screening for coloncancersiswidelyaccepted?Inamulticenteranalysisofuniversal tumor screening in colorectal cancer, 26 of 82 individuals (32%) with Lynch syndrome were diagnosed after age 60 years. 6 If we look at published data for endometrial cancer, we see relatively the same age distribution (38% to 42% of patients diagnosed after age 60 years). 2,4