Real-world uptake of Lynch syndrome testing among patients with mismatch repair-deficient endometrial cancer in Québec

MLH1

Mismatch repair deficiency (dMMR) detected by universal tumour immunohistochemistry, with predominant MLH1/PMS2 loss; exclusion of promoter hypermethylation points to a germline MMR pathogenic variant.

The authors assessed real-world follow-up of mismatch repair-deficient endometrial cancers screened by universal immunohistochemistry at a tertiary centre in Québec. Among 222 dMMR tumours, MLH1/PMS2 loss predominated. Seventy-four patients with methylation-negative tumours were eligible for Lynch syndrome evaluation: 73 (98.6%) were referred and 57 completed germline testing. A germline pathogenic variant was identified in 54.4% of them.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A 98.6% referral rate is unusual in the reflex screening literature, where attrition between immunohistochemistry and the genetics consultation is the usual breaking point; the result reflects the systematic nature of the chain rather than prescriber awareness. The 54.4% yield among methylation-negative patients who were tested is high and must be read alongside the sample size: 57 patients tested, with 16 lost between referral and testing. It is a single-centre series, but it documents precisely the step that universal screening programmes measure least.

Analysis by Dr Thibaut Benquey