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

Pauly, Nina; Baert, Thais; Schmutzler, Rita; du Bois, Andreas; Schneider, Stephanie; Rhiem, Kerstin; Schoemig-Markiefka, Birgid; Siemanowski, Janna; Heikaus, Sebastian; Traut, Alexander; Heitz, Florian; Prader, Sonia; Ehmann, Sarah; Harter, Philipp und Ataseven, Beyhan (2021): Modern day screening for Lynch syndrome in endometrial cancer: the KEM experience. In: Archives of Gynecology and Obstetrics, Bd. 304, Nr. 4: S. 975-984

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0932-0067
• Sprache: Englisch