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12.03.2021 | Gynecologic Oncology

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

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

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 4/2021

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Abstract

Purpose

Current guidelines for Lynch syndrome detection in endometrial cancer (EC) patients rely either on risk evaluation, based on personal/family history, or detection of mismatch repair (MMR) deficiency on tumor tissue. We present a combined screening algorithm for Lynch syndrome.

Methods

In this study, 213 consecutive patients treated for EC at Kliniken Essen-Mitte between 2014 and 2018 were included. Personal/family history was evaluated by the Amsterdam II, revised Bethesda/German-DKG criteria and prediction model PREMM₅. MMR testing was performed by immunohistochemistry (IHC) and/or polymerase chain reaction (PCR) based microsatellite analysis on tumor tissue. MLH1 promoter methylation analysis was performed in case of MLH1 loss or microsatellite instability.

Results

Based on personal/family history 2/213 (Amsterdam II), 31/213 (revised Bethesda/German-DKG) and 149/213 (PREMM₅) patients were identified as at risk for Lynch syndrome. MMR analysis was performed by IHC in 51.2%, by PCR in 32.4%, and in 16.4% of patients both methods were used. MMR deficiency was detected in 20.6% (44/213). Methylation analysis was performed in 27 patients of whom, 22 (81.4%) showed MLH1 promoter hypermethylation. Only 9% of MMR deficient patients were identified as at risk for Lynch syndrome by the revised Bethesda/German-DKG criteria. A pathogenic germline mutation was discovered in 3 out of 20 patients that underwent genetic testing. None of these patients were younger than 50 years or had a family history of Lynch syndrome-associated malignancies.

Conclusion

General MMR assessment is a feasible strategy to improve the detection of Lynch Syndrome in patients with EC.

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Titel: Modern day screening for Lynch syndrome in endometrial cancer: the KEM experience
verfasst von: Nina Pauly
Thaïs Baert
Rita Schmutzler
Andreas du Bois
Stephanie Schneider
Kerstin Rhiem
Birgid Schömig-Markiefka
Janna Siemanowski
Sebastian Heikaus
Alexander Traut
Florian Heitz
Sonia Prader
Sarah Ehmann
Philipp Harter
Beyhan Ataseven
Publikationsdatum: 12.03.2021
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 4/2021
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-021-06006-w

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