Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer <= 70 years

Celine Leenen, Margot Lier, Lena van Doorn, M Leerdam, SG Kooi, J de Waard, RF (Robert) Hoedemaeker, Ans van den Ouweland, Sanne Hulspas, Erik jan Dubbink, Ernst Kuipers, Anja Wagner, Winand Dinjens, Ewout Steyerberg

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Objective. Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (INC) staining for mismatch repair (MMR) proteins in tumour tissue of all newly diagnosed EC patients <= 70 years. Methods. Consecutive EC patients <= 70 years were included prospectively in eight Dutch centres. EC specimens were analysed for MSI. IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. tumours were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS). Results. Tumour specimens of 179 patients (median age 61 years, IQR 57-66) were analysed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50 years. In addition, 31 sporadic MSI-H tumours with MLH1 Conclusions. Molecular screening for LS in patients with EC diagnosed <= 70 years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50 years of age. (C) 2012 Elsevier Inc. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)414-420
Number of pages7
JournalGynecologic Oncology
Issue number2
Publication statusPublished - 2012

Research programs

  • EMC MGC-02-96-01
  • EMC MM-03-24-01
  • EMC MM-03-52-02-A
  • EMC MM-04-20-01
  • EMC NIHES-02-65-01

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