Modern day screening for Lynch syndrome in endometrial cancer: the KEM experience

Pauly, N; Baert, Thaïs; Schmutzler, Rita; Bois, Andreas du; Schneider, Stephanie; Rhiem, Kerstin; Schömig-Markiefka, Birgid; Siemanowski, Janna; Heikaus, Sebastian; Traut, Alexander; Heitz, Florian; Prader, Sonia; Ehmann, Sarah; Harter, Philipp; Ataseven, Beyhan

doi:10.1007/s00404-021-06006-w

Cited by 5 publications

(5 citation statements)

References 41 publications

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“…However, while immunohistochemical testing for MMR status was correctly performed in all patients, almost one-fifth (19.8%) of all MLH1-deficient patients did not undergo MLH1 promoter methylation testing and approximately one quarter (26.3%) of all patients suspected of having Lynch syndrome did not undergo genetic testing. In accordance with recent findings, the recommendation and implementation of genetic counseling and testing proved to be particularly error-prone and in need of improvement [24,[26][27][28]. Previous studies have shown that only about 60% of high-risk women with endometrial cancer are referred for genetic counseling, and only 35-40% undergo genetic testing [27,28].…”

Section: Main Findingssupporting

confidence: 52%

“…All such cases should be referred directly for genetic counseling within the scope of the multidisciplinary tumor board recommendation, with effective communication between healthcare professionals and a clear assignment of responsibilities being essential. In addition, the awareness and willingness of gynecologists to screen for Lynch syndrome needs to be increased and additional training may be required [26]. Genetic testing must be performed after genetic counseling and with the patient's general consent.…”

Section: Future Directionsmentioning

confidence: 99%

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

Joder,

Gmür,

Solass

et al. 2024

Cancers

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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.

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Section: Main Findingssupporting

confidence: 52%

Section: Future Directionsmentioning

confidence: 99%

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

Joder,

Gmür,

Solass

et al. 2024

Cancers

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“…Current guidelines for Lynch syndrome detection in endometrial cancer patients rely either on risk evaluation, based on personal/family history, or detection of MMR deficiency on tumor tissue [16] . Immunohistochemistry is a preferred method for Lynch syndrome screening in many laboratories due to its efficiency, relatively lower price and technical demands in comparison to other molecular techniques [17] .…”

Section: Discussionmentioning

confidence: 99%

Detection of Lynch Syndrome in Endometrial Cancer Patients

Kubelka Sabit,

Petrova,

Zhivadinoviкј

et al. 2023

AMJ

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Lynch syndrome (LS) is an autosomal dominant inherited disease defined by germline mutations in mismatch repair (MMR) genes, leading to a defective DNA MMR system. Patients with LS have predisposition to a spectrum of cancers, primarily colorectal cancer, but LS-associated endometrial cancer (LS-EC) is the most common extraintestinal cancer and occurs in 2% of LS patients. The most frequently mutated MMR genes are MLH1, MSH2, MSH6 and PMS2. Clinico-pathologic features of LS-EC are: early age of onset, lower body mass index, endometrioid type of carcinoma and lower uterine segment involvement.Recent studies support LS screening in every EC patient since MMR status is also part of the molecular subclassification of endometrial cancers. Screening methods include traditional clinical criteria and molecular techniques, such as MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1promoter methylation testing and gene sequencing. MSI can also be detected in sporadic tumors, through epigenetic events inactivating the MMR system.Patients with diagnosed LS and their affected relatives should be closely monitored in order to prevent the development of other types of cancer. Patients with advanced recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) endometrial cancer can also benefit from immunotherapy.We describe our 3-year experience in screening of Lynch syndrome in EC patients.

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“…On the other hand, Esteller et al, discovered that hMLH1 promoter hypermethylation and MSI were present in 11 of 12 (91%) instances of endometrial carcinoma [ 30 ]. An independent study by Pauly et al, demonstrated that there were 81.4% (22 out of 27) of endometrial carcinoma patients who had hMLH1 loss or microsatellite instability and showed hMLH1 promoter hypermethylation [ 31 ]. The aberrant expression of hMLH1 is undoubtedly linked to MSI, and DNA methylation of hMLH1 plays a critical role in the development of MSI.…”

Section: Tumor Suppressor Genesmentioning

confidence: 99%

Research Progress of DNA Methylation in Endometrial Cancer

Ding

Chen

et al. 2022

Biomolecules

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Endometrial cancer (EC)) is one of the most common malignant tumors of the female genital system, with an increasing incidence and mortality, worldwide. Although the therapeutic strategy of EC is still complicated and challenging, further understanding of carcinogenesis from a gene perspective would allow an effort to improve therapeutic precision in this complex malignancy. DNA methylation is the most widely studied epigenetic alteration in human tumors. Aberrant DNA methylation events, resulting in altered gene expression, are features of many tumor types. In this review, we provide an update on evidence about the roles of aberrant DNA methylation within some classical tumor suppressor genes and oncogenes in endometrial carcinogenesis, and report on recent advances in the understanding of the contribution of aberrant DNA methylation to EC, as well as opportunities and challenges of DNA methylation in EC management and prevention.

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Modern day screening for Lynch syndrome in endometrial cancer: the KEM experience

Cited by 5 publications

References 41 publications

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

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

Detection of Lynch Syndrome in Endometrial Cancer Patients

Research Progress of DNA Methylation in Endometrial Cancer

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