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. 2024 Feb 4;16(3):671.
doi: 10.3390/cancers16030671.

Real-World Data on Institutional Implementation of Screening for Mismatch Repair Deficiency and Lynch Syndrome in Endometrial Cancer Patients

Carmen Joder  1 , Andrea Gmür  2 , Wiebke Solass  3 , Lucine Christe  3 , Manuela Rabaglio  4 , Muriel Fluri  4 , Tilman T Rau  5 , Flurina A M Saner  2 , Laura Knabben  2 , Sara Imboden  2 , Michael D Mueller  2 , Franziska Siegenthaler  2
Affiliations

Real-World Data on Institutional Implementation of Screening for Mismatch Repair Deficiency and Lynch Syndrome in Endometrial Cancer Patients

Carmen Joder et al. Cancers (Basel). .

Abstract

Lynch syndrome is an inherited tumor syndrome caused by a pathogenic germline variant in DNA mismatch repair genes. As the leading cause of hereditary endometrial cancer, international guidelines recommend universal screening in women with endometrial cancer. However, testing for Lynch syndrome is not yet well established in clinical practice. The aim of this study was to evaluate adherence to our Lynch syndrome screening algorithm. A retrospective, single-center cohort study was conducted of all endometrial cancer patients undergoing surgical treatment at the Bern University Hospital, Switzerland, between 2017 and 2022. Adherence to immunohistochemical analysis of mismatch repair status, and, if indicated, to MLH1 promoter hypermethylation and to genetic counseling and testing was assessed. Of all 331 endometrial cancer patients, 102 (30.8%) were mismatch repair-deficient and 3 (0.9%) patients were diagnosed with Lynch syndrome. Overall screening adherence was 78.2%, with a notable improvement over the six years from 61.4% to 90.6%. A major reason for non-adherence was lack of provider recommendation for testing, with advanced patient age as a potential patient risk factor. Simplification of the algorithm through standardized reflex screening was recommended to provide optimal medical care for those affected and to allow for cascading testing of at-risk relatives.

Keywords: Lynch syndrome; endometrial cancer; genetic counseling; genetic testing; mismatch repair deficiency; quality control; reflex screening; testing adherence.

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Conflict of interest statement

All authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of Lynch syndrome screening algorithm at our institution. In accordance with the recommendations of the Manchester International Consensus Group [8] and AWMF [18]. Abbreviations: MMR—mismatch repair; EC—endometrial cancer.
Figure 2
Figure 2
Flowchart of adherence to Lynch syndrome screening algorithm at our institution. a MLH1/MSH2 loss was classified as both MLH1 and MSH2 loss. Abbreviations: N—number; MMR—mismatch repair; EC—endometrial cancer.
Figure 3
Figure 3
Development of testing adherence over the course of 2017 to 2022 in the patient cohort.
See this image and copyright information in PMC

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