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

• Published in: Archives of gynecology and obstetrics Vol. 304; no. 4; pp. 975 - 984
• Main Authors: Pauly, Nina, Baert, Thaïs, Schmutzler, Rita, du Bois, Andreas, Schneider, Stephanie, Rhiem, Kerstin, Schömig-Markiefka, Birgid, Siemanowski, Janna, Heikaus, Sebastian, Traut, Alexander, Heitz, Florian, Prader, Sonia, Ehmann, Sarah, Harter, Philipp, Ataseven, Beyhan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2021; Springer Nature B.V
• Subjects: Antibodies; Cell division; Colorectal cancer; DNA methylation; Endocrinology; Endometrial cancer; Family medical history; Genetic disorders; Gynecologic Oncology; Gynecology; Human Genetics; Medicine; Medicine & Public Health; Mutation; Obstetrics/Perinatology/Midwifery; Oncology; Ovarian cancer; Patients; Polymerase chain reaction; Protein expression; Endometrial cancer; MLH1 hypermethylation; DNA mismatch repair; Lynch syndrome
• ISSN: 0932-0067; 1432-0711; 1432-0711
• DOI: 10.1007/s00404-021-06006-w

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 PREMM 5 . 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 (PREMM 5 ) 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.