The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis

Abstract

Purpose

Endometrial cancer (EC) is often the sentinel cancer in women with Lynch syndrome (LS). However, efforts to implement universal LS screening in EC patients have been hampered by a lack of evidence detailing the proportion of EC patients that would be expected to screen positive for LS.

Methods

Studies were identified by electronic searches of Medline, Embase, Cochrane CENTRAL and Web of Science. Proportions of test positivity were calculated by random and fixed-effects meta-analysis models. I ² score was used to assess heterogeneity across studies.

Results

Fifty-three studies, including 12,633 EC patients, met the inclusion criteria. The overall proportion of endometrial tumors with microsatellite instability or mismatch repair (MMR) deficiency by immunohistochemistry (IHC) was 0.27 (95% confidence interval [CI] 0.25–0.28, I ²: 71%) and 0.26 (95% CI 0.25–0.27, I ²: 88%), respectively. Of those women with abnormal tumor testing, 0.29 (95% CI 0.25–0.33, I ²: 83%) had LS-associated pathogenic variants on germline testing; therefore around 3% of ECs can be attributed to LS. Preselection of EC cases did increase the proportion of germline LS diagnoses.

Conclusion

The current study suggests that prevalence of LS in EC patients is approximately 3%, similar to that of colorectal cancer patients; therefore our data support the implementation of universal EC screening for LS.